Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.1674del (p.Gly559fs)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Sep 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.1674del (p.Gly559fs)
Variation ID: 37425 Accession: VCV000037425.34
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093857 (GRCh38) [ NCBI UCSC ] 17: 41245874 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Nov 24, 2024 Sep 8, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.1674del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gly559fs frameshift NM_001407571.1:c.1461del NP_001394500.1:p.Gly488fs frameshift NM_001407581.1:c.1674del NP_001394510.1:p.Gly559fs frameshift NM_001407582.1:c.1674del NP_001394511.1:p.Gly559fs frameshift NM_001407583.1:c.1674del NP_001394512.1:p.Gly559fs frameshift NM_001407585.1:c.1674del NP_001394514.1:p.Gly559fs frameshift NM_001407587.1:c.1671del NP_001394516.1:p.Gly558fs frameshift NM_001407590.1:c.1671del NP_001394519.1:p.Gly558fs frameshift NM_001407591.1:c.1671del NP_001394520.1:p.Gly558fs frameshift NM_001407593.1:c.1674del NP_001394522.1:p.Gly559fs frameshift NM_001407594.1:c.1674del NP_001394523.1:p.Gly559fs frameshift NM_001407596.1:c.1674del NP_001394525.1:p.Gly559fs frameshift NM_001407597.1:c.1674del NP_001394526.1:p.Gly559fs frameshift NM_001407598.1:c.1674del NP_001394527.1:p.Gly559fs frameshift NM_001407602.1:c.1674del NP_001394531.1:p.Gly559fs frameshift NM_001407603.1:c.1674del NP_001394532.1:p.Gly559fs frameshift NM_001407605.1:c.1674del NP_001394534.1:p.Gly559fs frameshift NM_001407610.1:c.1671del NP_001394539.1:p.Gly558fs frameshift NM_001407611.1:c.1671del NP_001394540.1:p.Gly558fs frameshift NM_001407612.1:c.1671del NP_001394541.1:p.Gly558fs frameshift NM_001407613.1:c.1671del NP_001394542.1:p.Gly558fs frameshift NM_001407614.1:c.1671del NP_001394543.1:p.Gly558fs frameshift NM_001407615.1:c.1671del NP_001394544.1:p.Gly558fs frameshift NM_001407616.1:c.1674del NP_001394545.1:p.Gly559fs frameshift NM_001407617.1:c.1674del NP_001394546.1:p.Gly559fs frameshift NM_001407618.1:c.1674del NP_001394547.1:p.Gly559fs frameshift NM_001407619.1:c.1674del NP_001394548.1:p.Gly559fs frameshift NM_001407620.1:c.1674del NP_001394549.1:p.Gly559fs frameshift NM_001407621.1:c.1674del NP_001394550.1:p.Gly559fs frameshift NM_001407622.1:c.1674del NP_001394551.1:p.Gly559fs frameshift NM_001407623.1:c.1674del NP_001394552.1:p.Gly559fs frameshift NM_001407624.1:c.1674del NP_001394553.1:p.Gly559fs frameshift NM_001407625.1:c.1674del NP_001394554.1:p.Gly559fs frameshift NM_001407626.1:c.1674del NP_001394555.1:p.Gly559fs frameshift NM_001407627.1:c.1671del NP_001394556.1:p.Gly558fs frameshift NM_001407628.1:c.1671del NP_001394557.1:p.Gly558fs frameshift NM_001407629.1:c.1671del NP_001394558.1:p.Gly558fs frameshift NM_001407630.1:c.1671del NP_001394559.1:p.Gly558fs frameshift NM_001407631.1:c.1671del NP_001394560.1:p.Gly558fs frameshift NM_001407632.1:c.1671del NP_001394561.1:p.Gly558fs frameshift NM_001407633.1:c.1671del NP_001394562.1:p.Gly558fs frameshift NM_001407634.1:c.1671del NP_001394563.1:p.Gly558fs frameshift NM_001407635.1:c.1671del NP_001394564.1:p.Gly558fs frameshift NM_001407636.1:c.1671del NP_001394565.1:p.Gly558fs frameshift NM_001407637.1:c.1671del NP_001394566.1:p.Gly558fs frameshift NM_001407638.1:c.1671del NP_001394567.1:p.Gly558fs frameshift NM_001407639.1:c.1674del NP_001394568.1:p.Gly559fs frameshift NM_001407640.1:c.1674del NP_001394569.1:p.Gly559fs frameshift NM_001407641.1:c.1674del NP_001394570.1:p.Gly559fs frameshift NM_001407642.1:c.1674del NP_001394571.1:p.Gly559fs frameshift NM_001407644.1:c.1671del NP_001394573.1:p.Gly558fs frameshift NM_001407645.1:c.1671del NP_001394574.1:p.Gly558fs frameshift NM_001407646.1:c.1665del NP_001394575.1:p.Gly556fs frameshift NM_001407647.1:c.1665del NP_001394576.1:p.Gly556fs frameshift NM_001407648.1:c.1551del NP_001394577.1:p.Gly518fs frameshift NM_001407649.1:c.1548del NP_001394578.1:p.Gly517fs frameshift NM_001407652.1:c.1674del NP_001394581.1:p.Gly559fs frameshift NM_001407653.1:c.1596del NP_001394582.1:p.Gly533fs frameshift NM_001407654.1:c.1596del NP_001394583.1:p.Gly533fs frameshift NM_001407655.1:c.1596del NP_001394584.1:p.Gly533fs frameshift NM_001407656.1:c.1596del NP_001394585.1:p.Gly533fs frameshift NM_001407657.1:c.1596del NP_001394586.1:p.Gly533fs frameshift NM_001407658.1:c.1596del NP_001394587.1:p.Gly533fs frameshift NM_001407659.1:c.1593del NP_001394588.1:p.Gly532fs frameshift NM_001407660.1:c.1593del NP_001394589.1:p.Gly532fs frameshift NM_001407661.1:c.1593del NP_001394590.1:p.Gly532fs frameshift NM_001407662.1:c.1593del NP_001394591.1:p.Gly532fs frameshift NM_001407663.1:c.1596del NP_001394592.1:p.Gly533fs frameshift NM_001407664.1:c.1551del NP_001394593.1:p.Gly518fs frameshift NM_001407665.1:c.1551del NP_001394594.1:p.Gly518fs frameshift NM_001407666.1:c.1551del NP_001394595.1:p.Gly518fs frameshift NM_001407667.1:c.1551del NP_001394596.1:p.Gly518fs frameshift NM_001407668.1:c.1551del NP_001394597.1:p.Gly518fs frameshift NM_001407669.1:c.1551del NP_001394598.1:p.Gly518fs frameshift NM_001407670.1:c.1548del NP_001394599.1:p.Gly517fs frameshift NM_001407671.1:c.1548del NP_001394600.1:p.Gly517fs frameshift NM_001407672.1:c.1548del NP_001394601.1:p.Gly517fs frameshift NM_001407673.1:c.1548del NP_001394602.1:p.Gly517fs frameshift NM_001407674.1:c.1551del NP_001394603.1:p.Gly518fs frameshift NM_001407675.1:c.1551del NP_001394604.1:p.Gly518fs frameshift NM_001407676.1:c.1551del NP_001394605.1:p.Gly518fs frameshift NM_001407677.1:c.1551del NP_001394606.1:p.Gly518fs frameshift NM_001407678.1:c.1551del NP_001394607.1:p.Gly518fs frameshift NM_001407679.1:c.1551del NP_001394608.1:p.Gly518fs frameshift NM_001407680.1:c.1551del NP_001394609.1:p.Gly518fs frameshift NM_001407681.1:c.1551del NP_001394610.1:p.Gly518fs frameshift NM_001407682.1:c.1551del NP_001394611.1:p.Gly518fs frameshift NM_001407683.1:c.1551del NP_001394612.1:p.Gly518fs frameshift NM_001407684.1:c.1674del NP_001394613.1:p.Gly559fs frameshift NM_001407685.1:c.1548del NP_001394614.1:p.Gly517fs frameshift NM_001407686.1:c.1548del NP_001394615.1:p.Gly517fs frameshift NM_001407687.1:c.1548del NP_001394616.1:p.Gly517fs frameshift NM_001407688.1:c.1548del NP_001394617.1:p.Gly517fs frameshift NM_001407689.1:c.1548del NP_001394618.1:p.Gly517fs frameshift NM_001407690.1:c.1548del NP_001394619.1:p.Gly517fs frameshift NM_001407691.1:c.1548del NP_001394620.1:p.Gly517fs frameshift NM_001407692.1:c.1533del NP_001394621.1:p.Gly512fs frameshift NM_001407694.1:c.1533del NP_001394623.1:p.Gly512fs frameshift NM_001407695.1:c.1533del NP_001394624.1:p.Gly512fs frameshift NM_001407696.1:c.1533del NP_001394625.1:p.Gly512fs frameshift NM_001407697.1:c.1533del NP_001394626.1:p.Gly512fs frameshift NM_001407698.1:c.1533del NP_001394627.1:p.Gly512fs frameshift NM_001407724.1:c.1533del NP_001394653.1:p.Gly512fs frameshift NM_001407725.1:c.1533del NP_001394654.1:p.Gly512fs frameshift NM_001407726.1:c.1533del NP_001394655.1:p.Gly512fs frameshift NM_001407727.1:c.1533del NP_001394656.1:p.Gly512fs frameshift NM_001407728.1:c.1533del NP_001394657.1:p.Gly512fs frameshift NM_001407729.1:c.1533del NP_001394658.1:p.Gly512fs frameshift NM_001407730.1:c.1533del NP_001394659.1:p.Gly512fs frameshift NM_001407731.1:c.1533del NP_001394660.1:p.Gly512fs frameshift NM_001407732.1:c.1533del NP_001394661.1:p.Gly512fs frameshift NM_001407733.1:c.1533del NP_001394662.1:p.Gly512fs frameshift NM_001407734.1:c.1533del NP_001394663.1:p.Gly512fs frameshift NM_001407735.1:c.1533del NP_001394664.1:p.Gly512fs frameshift NM_001407736.1:c.1533del NP_001394665.1:p.Gly512fs frameshift NM_001407737.1:c.1533del NP_001394666.1:p.Gly512fs frameshift NM_001407738.1:c.1533del NP_001394667.1:p.Gly512fs frameshift NM_001407739.1:c.1533del NP_001394668.1:p.Gly512fs frameshift NM_001407740.1:c.1530del NP_001394669.1:p.Gly511fs frameshift NM_001407741.1:c.1530del NP_001394670.1:p.Gly511fs frameshift NM_001407742.1:c.1530del NP_001394671.1:p.Gly511fs frameshift NM_001407743.1:c.1530del NP_001394672.1:p.Gly511fs frameshift NM_001407744.1:c.1530del NP_001394673.1:p.Gly511fs frameshift NM_001407745.1:c.1530del NP_001394674.1:p.Gly511fs frameshift NM_001407746.1:c.1530del NP_001394675.1:p.Gly511fs frameshift NM_001407747.1:c.1530del NP_001394676.1:p.Gly511fs frameshift NM_001407748.1:c.1530del NP_001394677.1:p.Gly511fs frameshift NM_001407749.1:c.1530del NP_001394678.1:p.Gly511fs frameshift NM_001407750.1:c.1533del NP_001394679.1:p.Gly512fs frameshift NM_001407751.1:c.1533del NP_001394680.1:p.Gly512fs frameshift NM_001407752.1:c.1533del NP_001394681.1:p.Gly512fs frameshift NM_001407838.1:c.1530del NP_001394767.1:p.Gly511fs frameshift NM_001407839.1:c.1530del NP_001394768.1:p.Gly511fs frameshift NM_001407841.1:c.1530del NP_001394770.1:p.Gly511fs frameshift NM_001407842.1:c.1530del NP_001394771.1:p.Gly511fs frameshift NM_001407843.1:c.1530del NP_001394772.1:p.Gly511fs frameshift NM_001407844.1:c.1530del NP_001394773.1:p.Gly511fs frameshift NM_001407845.1:c.1530del NP_001394774.1:p.Gly511fs frameshift NM_001407846.1:c.1530del NP_001394775.1:p.Gly511fs frameshift NM_001407847.1:c.1530del NP_001394776.1:p.Gly511fs frameshift NM_001407848.1:c.1530del NP_001394777.1:p.Gly511fs frameshift NM_001407849.1:c.1530del NP_001394778.1:p.Gly511fs frameshift NM_001407850.1:c.1533del NP_001394779.1:p.Gly512fs frameshift NM_001407851.1:c.1533del NP_001394780.1:p.Gly512fs frameshift NM_001407852.1:c.1533del NP_001394781.1:p.Gly512fs frameshift NM_001407853.1:c.1461del NP_001394782.1:p.Gly488fs frameshift NM_001407854.1:c.1674del NP_001394783.1:p.Gly559fs frameshift NM_001407858.1:c.1674del NP_001394787.1:p.Gly559fs frameshift NM_001407859.1:c.1674del NP_001394788.1:p.Gly559fs frameshift NM_001407860.1:c.1671del NP_001394789.1:p.Gly558fs frameshift NM_001407861.1:c.1671del NP_001394790.1:p.Gly558fs frameshift NM_001407862.1:c.1473del NP_001394791.1:p.Gly492fs frameshift NM_001407863.1:c.1551del NP_001394792.1:p.Gly518fs frameshift NM_001407874.1:c.1470del NP_001394803.1:p.Gly491fs frameshift NM_001407875.1:c.1470del NP_001394804.1:p.Gly491fs frameshift NM_001407879.1:c.1464del NP_001394808.1:p.Gly489fs frameshift NM_001407881.1:c.1464del NP_001394810.1:p.Gly489fs frameshift NM_001407882.1:c.1464del NP_001394811.1:p.Gly489fs frameshift NM_001407884.1:c.1464del NP_001394813.1:p.Gly489fs frameshift NM_001407885.1:c.1464del NP_001394814.1:p.Gly489fs frameshift NM_001407886.1:c.1464del NP_001394815.1:p.Gly489fs frameshift NM_001407887.1:c.1464del NP_001394816.1:p.Gly489fs frameshift NM_001407889.1:c.1464del NP_001394818.1:p.Gly489fs frameshift NM_001407894.1:c.1461del NP_001394823.1:p.Gly488fs frameshift NM_001407895.1:c.1461del NP_001394824.1:p.Gly488fs frameshift NM_001407896.1:c.1461del NP_001394825.1:p.Gly488fs frameshift NM_001407897.1:c.1461del NP_001394826.1:p.Gly488fs frameshift NM_001407898.1:c.1461del NP_001394827.1:p.Gly488fs frameshift NM_001407899.1:c.1461del NP_001394828.1:p.Gly488fs frameshift NM_001407900.1:c.1464del NP_001394829.1:p.Gly489fs frameshift NM_001407902.1:c.1464del NP_001394831.1:p.Gly489fs frameshift NM_001407904.1:c.1464del NP_001394833.1:p.Gly489fs frameshift NM_001407906.1:c.1464del NP_001394835.1:p.Gly489fs frameshift NM_001407907.1:c.1464del NP_001394836.1:p.Gly489fs frameshift NM_001407908.1:c.1464del NP_001394837.1:p.Gly489fs frameshift NM_001407909.1:c.1464del NP_001394838.1:p.Gly489fs frameshift NM_001407910.1:c.1464del NP_001394839.1:p.Gly489fs frameshift NM_001407915.1:c.1461del NP_001394844.1:p.Gly488fs frameshift NM_001407916.1:c.1461del NP_001394845.1:p.Gly488fs frameshift NM_001407917.1:c.1461del NP_001394846.1:p.Gly488fs frameshift NM_001407918.1:c.1461del NP_001394847.1:p.Gly488fs frameshift NM_001407919.1:c.1551del NP_001394848.1:p.Gly518fs frameshift NM_001407920.1:c.1410del NP_001394849.1:p.Gly471fs frameshift NM_001407921.1:c.1410del NP_001394850.1:p.Gly471fs frameshift NM_001407922.1:c.1410del NP_001394851.1:p.Gly471fs frameshift NM_001407923.1:c.1410del NP_001394852.1:p.Gly471fs frameshift NM_001407924.1:c.1410del NP_001394853.1:p.Gly471fs frameshift NM_001407925.1:c.1410del NP_001394854.1:p.Gly471fs frameshift NM_001407926.1:c.1410del NP_001394855.1:p.Gly471fs frameshift NM_001407927.1:c.1410del NP_001394856.1:p.Gly471fs frameshift NM_001407928.1:c.1410del NP_001394857.1:p.Gly471fs frameshift NM_001407929.1:c.1410del NP_001394858.1:p.Gly471fs frameshift NM_001407930.1:c.1407del NP_001394859.1:p.Gly470fs frameshift NM_001407931.1:c.1407del NP_001394860.1:p.Gly470fs frameshift NM_001407932.1:c.1407del NP_001394861.1:p.Gly470fs frameshift NM_001407933.1:c.1410del NP_001394862.1:p.Gly471fs frameshift NM_001407934.1:c.1407del NP_001394863.1:p.Gly470fs frameshift NM_001407935.1:c.1410del NP_001394864.1:p.Gly471fs frameshift NM_001407936.1:c.1407del NP_001394865.1:p.Gly470fs frameshift NM_001407937.1:c.1551del NP_001394866.1:p.Gly518fs frameshift NM_001407938.1:c.1551del NP_001394867.1:p.Gly518fs frameshift NM_001407939.1:c.1551del NP_001394868.1:p.Gly518fs frameshift NM_001407940.1:c.1548del NP_001394869.1:p.Gly517fs frameshift NM_001407941.1:c.1548del NP_001394870.1:p.Gly517fs frameshift NM_001407942.1:c.1533del NP_001394871.1:p.Gly512fs frameshift NM_001407943.1:c.1530del NP_001394872.1:p.Gly511fs frameshift NM_001407944.1:c.1533del NP_001394873.1:p.Gly512fs frameshift NM_001407945.1:c.1533del NP_001394874.1:p.Gly512fs frameshift NM_001407946.1:c.1341del NP_001394875.1:p.Gly448fs frameshift NM_001407947.1:c.1341del NP_001394876.1:p.Gly448fs frameshift NM_001407948.1:c.1341del NP_001394877.1:p.Gly448fs frameshift NM_001407949.1:c.1341del NP_001394878.1:p.Gly448fs frameshift NM_001407950.1:c.1341del NP_001394879.1:p.Gly448fs frameshift NM_001407951.1:c.1341del NP_001394880.1:p.Gly448fs frameshift NM_001407952.1:c.1341del NP_001394881.1:p.Gly448fs frameshift NM_001407953.1:c.1341del NP_001394882.1:p.Gly448fs frameshift NM_001407954.1:c.1338del NP_001394883.1:p.Gly447fs frameshift NM_001407955.1:c.1338del NP_001394884.1:p.Gly447fs frameshift NM_001407956.1:c.1338del NP_001394885.1:p.Gly447fs frameshift NM_001407957.1:c.1341del NP_001394886.1:p.Gly448fs frameshift NM_001407958.1:c.1338del NP_001394887.1:p.Gly447fs frameshift NM_001407959.1:c.1293del NP_001394888.1:p.Gly432fs frameshift NM_001407960.1:c.1293del NP_001394889.1:p.Gly432fs frameshift NM_001407962.1:c.1290del NP_001394891.1:p.Gly431fs frameshift NM_001407963.1:c.1293del NP_001394892.1:p.Gly432fs frameshift NM_001407964.1:c.1530del NP_001394893.1:p.Gly511fs frameshift NM_001407965.1:c.1170del NP_001394894.1:p.Gly391fs frameshift NM_001407966.1:c.786del NP_001394895.1:p.Gly263fs frameshift NM_001407967.1:c.786del NP_001394896.1:p.Gly263fs frameshift NM_001407968.1:c.787+887del intron variant NM_001407969.1:c.787+887del intron variant NM_001407970.1:c.787+887del intron variant NM_001407971.1:c.787+887del intron variant NM_001407972.1:c.784+887del intron variant NM_001407973.1:c.787+887del intron variant NM_001407974.1:c.787+887del intron variant NM_001407975.1:c.787+887del intron variant NM_001407976.1:c.787+887del intron variant NM_001407977.1:c.787+887del intron variant NM_001407978.1:c.787+887del intron variant NM_001407979.1:c.787+887del intron variant NM_001407980.1:c.787+887del intron variant NM_001407981.1:c.787+887del intron variant NM_001407982.1:c.787+887del intron variant NM_001407983.1:c.787+887del intron variant NM_001407984.1:c.784+887del intron variant NM_001407985.1:c.784+887del intron variant NM_001407986.1:c.784+887del intron variant NM_001407990.1:c.787+887del intron variant NM_001407991.1:c.784+887del intron variant NM_001407992.1:c.784+887del intron variant NM_001407993.1:c.787+887del intron variant NM_001408392.1:c.784+887del intron variant NM_001408396.1:c.784+887del intron variant NM_001408397.1:c.784+887del intron variant NM_001408398.1:c.784+887del intron variant NM_001408399.1:c.784+887del intron variant NM_001408400.1:c.784+887del intron variant NM_001408401.1:c.784+887del intron variant NM_001408402.1:c.784+887del intron variant NM_001408403.1:c.787+887del intron variant NM_001408404.1:c.787+887del intron variant NM_001408406.1:c.790+884del intron variant NM_001408407.1:c.784+887del intron variant NM_001408408.1:c.778+887del intron variant NM_001408409.1:c.709+887del intron variant NM_001408410.1:c.646+887del intron variant NM_001408411.1:c.709+887del intron variant NM_001408412.1:c.709+887del intron variant NM_001408413.1:c.706+887del intron variant NM_001408414.1:c.709+887del intron variant NM_001408415.1:c.709+887del intron variant NM_001408416.1:c.706+887del intron variant NM_001408418.1:c.670+1989del intron variant NM_001408419.1:c.670+1989del intron variant NM_001408420.1:c.670+1989del intron variant NM_001408421.1:c.667+1989del intron variant NM_001408422.1:c.670+1989del intron variant NM_001408423.1:c.670+1989del intron variant NM_001408424.1:c.667+1989del intron variant NM_001408425.1:c.664+887del intron variant NM_001408426.1:c.664+887del intron variant NM_001408427.1:c.664+887del intron variant NM_001408428.1:c.664+887del intron variant NM_001408429.1:c.664+887del intron variant NM_001408430.1:c.664+887del intron variant NM_001408431.1:c.667+1989del intron variant NM_001408432.1:c.661+887del intron variant NM_001408433.1:c.661+887del intron variant NM_001408434.1:c.661+887del intron variant NM_001408435.1:c.661+887del intron variant NM_001408436.1:c.664+887del intron variant NM_001408437.1:c.664+887del intron variant NM_001408438.1:c.664+887del intron variant NM_001408439.1:c.664+887del intron variant NM_001408440.1:c.664+887del intron variant NM_001408441.1:c.664+887del intron variant NM_001408442.1:c.664+887del intron variant NM_001408443.1:c.664+887del intron variant NM_001408444.1:c.664+887del intron variant NM_001408445.1:c.661+887del intron variant NM_001408446.1:c.661+887del intron variant NM_001408447.1:c.661+887del intron variant NM_001408448.1:c.661+887del intron variant NM_001408450.1:c.661+887del intron variant NM_001408451.1:c.652+887del intron variant NM_001408452.1:c.646+887del intron variant NM_001408453.1:c.646+887del intron variant NM_001408454.1:c.646+887del intron variant NM_001408455.1:c.646+887del intron variant NM_001408456.1:c.646+887del intron variant NM_001408457.1:c.646+887del intron variant NM_001408458.1:c.646+887del intron variant NM_001408459.1:c.646+887del intron variant NM_001408460.1:c.646+887del intron variant NM_001408461.1:c.646+887del intron variant NM_001408462.1:c.643+887del intron variant NM_001408463.1:c.643+887del intron variant NM_001408464.1:c.643+887del intron variant NM_001408465.1:c.643+887del intron variant NM_001408466.1:c.646+887del intron variant NM_001408467.1:c.646+887del intron variant NM_001408468.1:c.643+887del intron variant NM_001408469.1:c.646+887del intron variant NM_001408470.1:c.643+887del intron variant NM_001408472.1:c.787+887del intron variant NM_001408473.1:c.784+887del intron variant NM_001408474.1:c.586+887del intron variant NM_001408475.1:c.583+887del intron variant NM_001408476.1:c.586+887del intron variant NM_001408478.1:c.577+887del intron variant NM_001408479.1:c.577+887del intron variant NM_001408480.1:c.577+887del intron variant NM_001408481.1:c.577+887del intron variant NM_001408482.1:c.577+887del intron variant NM_001408483.1:c.577+887del intron variant NM_001408484.1:c.577+887del intron variant NM_001408485.1:c.577+887del intron variant NM_001408489.1:c.577+887del intron variant NM_001408490.1:c.574+887del intron variant NM_001408491.1:c.574+887del intron variant NM_001408492.1:c.577+887del intron variant NM_001408493.1:c.574+887del intron variant NM_001408494.1:c.548-2825del intron variant NM_001408495.1:c.545-2825del intron variant NM_001408496.1:c.523+887del intron variant NM_001408497.1:c.523+887del intron variant NM_001408498.1:c.523+887del intron variant NM_001408499.1:c.523+887del intron variant NM_001408500.1:c.523+887del intron variant NM_001408501.1:c.523+887del intron variant NM_001408502.1:c.454+887del intron variant NM_001408503.1:c.520+887del intron variant NM_001408504.1:c.520+887del intron variant NM_001408505.1:c.520+887del intron variant NM_001408506.1:c.460+1989del intron variant NM_001408507.1:c.460+1989del intron variant NM_001408508.1:c.451+887del intron variant NM_001408509.1:c.451+887del intron variant NM_001408510.1:c.406+887del intron variant NM_001408511.1:c.404-2825del intron variant NM_001408512.1:c.283+887del intron variant NM_001408513.1:c.577+887del intron variant NM_001408514.1:c.577+887del intron variant NM_007294.3:c.1674delA frameshift NM_007297.4:c.1533del NP_009228.2:p.Gly512fs frameshift NM_007298.4:c.787+887del intron variant NM_007299.4:c.787+887del intron variant NM_007300.4:c.1674del NP_009231.2:p.Gly559fs frameshift NR_027676.1:n.1807delA NC_000017.11:g.43093860del NC_000017.10:g.41245877del NG_005905.2:g.124127del LRG_292:g.124127del LRG_292t1:c.1671del LRG_292p1:p.Gly559Valfs U14680.1:n.1793delA - Protein change
- G559fs, G512fs, G432fs, G470fs, G489fs, G518fs, G558fs, G263fs, G491fs, G492fs, G532fs, G556fs, G448fs, G511fs, G391fs, G431fs, G447fs, G471fs, G488fs, G517fs, G533fs
- Other names
-
p.Gly559ValfsTer13
1793delA
- Canonical SPDI
- NC_000017.11:43093856:TTTT:TTT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13071 | 14880 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (7) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000031006.19 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 5, 2024 | RCV000047556.23 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Feb 23, 2017 | RCV000470654.9 | |
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jul 23, 2024 | RCV000486975.23 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 2, 2024 | RCV000580485.16 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 7, 2023 | RCV003389314.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Sep 08, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000299634.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Feb 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Baylor Genetics
Accession: SCV000540950.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
Number of individuals with the variant: 1
|
|
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Pathogenic
(Aug 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361785.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: BRCA1 c.1674delA (p.Gly559ValfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.1674delA (p.Gly559ValfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250426 control chromosomes (gnomAD). c.1674delA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submissions (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
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Pathogenic
(Nov 16, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000682976.3
First in ClinVar: Feb 19, 2018 Last updated: Jun 19, 2021 |
Comment:
This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 11773283, 23479189, 23683081, 28680148, 28528518). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Mar 11, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600261.3
First in ClinVar: Sep 28, 2017 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been identified in individuals with breast cancer and ovarian cancer … (more)
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been identified in individuals with breast cancer and ovarian cancer in the published literature (PMID: 31921681 (2019), 29446198 (2018), 28680148 (2017), 22044689 (2012), 11773283 (2002), 9145677 (1997)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Feb 03, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004215113.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Apr 02, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001173079.5
First in ClinVar: Mar 16, 2020 Last updated: Aug 11, 2024 |
Comment:
The c.1674delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1674, causing … (more)
The c.1674delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1674, causing a translational frameshift with a predicted alternate stop codon (p.G559Vfs*13). This mutation has been reported in patients with personal and/or family histories suspicious for Hereditary Breast and Ovarian Cancer (Couch FJ et al. N. Engl. J. Med. 1997 May;336:1409-15; Geisler JP et al. J Natl Cancer Inst, 2002 Jan;94:61-7; Shih HA et al. J Clin Oncol, 2002 Feb;20:994-9; Dworkin AM et al. Fam Cancer, 2009 Apr;8:339-46; Rodríguez AO et al. Gynecol Oncol, 2012 Feb;124:236-43; Blay P et al. BMC Cancer. 2013 May;13:243; de Juan Jiménez I et al. Fam Cancer, 2013 Dec;12:767-77; Briceño-Balcázar I et al. Colomb Med (Cali), 2017 Jun;48:58-63; Torres D et al. Sci Rep, 2017 07;7:4713 Cock-Rada AM et al. Fam Cancer, 2018 01;17:23-30; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620; Wei H et al. Oncol Lett, 2018 Jun;15:9420-9428; Li JY et al. Int J Cancer, 2019 01;144:281-289; Oliver J et al. Front Oncol, 2019 Dec;9:1429). Of note, this alteration has also been reported as 1790delA and 1793delA in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Nov 14, 2017)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000785551.2
First in ClinVar: Nov 05, 2016 Last updated: Nov 05, 2016 |
|
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Pathogenic
(Jun 03, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: yes
Allele origin:
germline
|
AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002502698.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: yes
|
|
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Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000325121.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
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Pathogenic
(Jul 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000568426.6
First in ClinVar: Apr 27, 2017 Last updated: Jul 22, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in association with hereditary breast and ovarian cancer (Geisler et al., 2002; Dworkin et al., 2009; Rodriguez et al., 2012; Blay et al., 2013; de Juan Jimenez et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 1793delA; This variant is associated with the following publications: (PMID: 31921681, 11304778, 11773283, 31825140, 34413315, 23683081, 23479189, 9145677, 19340607, 22044689, 16267036, 28024868, 29659587, 28528518, 29752822) (less)
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Pathogenic
(Nov 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: yes
Allele origin:
germline
|
Molecular Genetics and NGS Laboratory, Hospital Fundacion Valle Del Lili
Accession: SCV004101392.1
First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 2023 |
Number of individuals with the variant: 12
Age: 30-50 years
Sex: female
Ethnicity/Population group: Latin
Geographic origin: Colombia
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Pathogenic
(Oct 03, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002017906.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
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Pathogenic
(Jan 05, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000075569.12
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gly559Valfs*13) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gly559Valfs*13) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 9145677, 11773283, 23479189, 23683081). This variant is also known as 1790delA and 1793delA. ClinVar contains an entry for this variant (Variation ID: 37425). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 23, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV005413237.1
First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024 |
Comment:
PM2, PM5_strong, PVS1
Number of individuals with the variant: 1
|
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Pathogenic
(Jul 16, 2010)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053599.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
|
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Pathogenic
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587156.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550743.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The BRCA1 p.Gly559Valfs*13 variant was identified in 5 of 5020 proband chromosomes (frequency: 0.001) from individuals or families with non-hereditary diffuse gastric cancer, breast or … (more)
The BRCA1 p.Gly559Valfs*13 variant was identified in 5 of 5020 proband chromosomes (frequency: 0.001) from individuals or families with non-hereditary diffuse gastric cancer, breast or ovarian cancer and was not identified in 2340 chromosomes from population-matched controls (Blay 2013, Couch 1997, de Juan Jimenez 2013, Sahasrabudhe 2017, Torres 2017). The variant was also identified in dbSNP (ID: rs80357600) as "With Pathogenic allele", ClinVar (classified as pathogenic by Invitae, GeneDx, and nine other submitters), COGR (1x pathogenic), LOVD 3.0 (6x pathogenic), BIC Database (6x with clinical importance), and in ARUP Laboratories database (definitely pathogenic). The variant was not identified in Cosmic, UMD-LSDB, or Zhejiang University databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The c.1674del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 559 and leads to a premature stop codon at position 571. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer (HBOC) syndrome and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Pathogenic
(May 24, 2021)
|
no assertion criteria provided
Method: case-control
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Molecular Oncology, Hospital Universitario Central de Asturias (HUCA)
Accession: SCV005061278.1
First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024 |
Secondary finding: no
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Pathogenic
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144153.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 2
Observation 2:
Number of individuals with the variant: 4
Ethnicity/Population group: Latin American, Caribbean
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Comment:
Comment:
Variant summary: BRCA1 c.1674delA (p.Gly559ValfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250426 control chromosomes (gnomAD). c.1674delA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submissions (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 11773283, 23479189, 23683081, 28680148, 28528518). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been identified in individuals with breast cancer and ovarian cancer in the published literature (PMID: 31921681 (2019), 29446198 (2018), 28680148 (2017), 22044689 (2012), 11773283 (2002), 9145677 (1997)). Based on the available information, this variant is classified as pathogenic.
Comment:
The c.1674delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1674, causing a translational frameshift with a predicted alternate stop codon (p.G559Vfs*13). This mutation has been reported in patients with personal and/or family histories suspicious for Hereditary Breast and Ovarian Cancer (Couch FJ et al. N. Engl. J. Med. 1997 May;336:1409-15; Geisler JP et al. J Natl Cancer Inst, 2002 Jan;94:61-7; Shih HA et al. J Clin Oncol, 2002 Feb;20:994-9; Dworkin AM et al. Fam Cancer, 2009 Apr;8:339-46; Rodríguez AO et al. Gynecol Oncol, 2012 Feb;124:236-43; Blay P et al. BMC Cancer. 2013 May;13:243; de Juan Jiménez I et al. Fam Cancer, 2013 Dec;12:767-77; Briceño-Balcázar I et al. Colomb Med (Cali), 2017 Jun;48:58-63; Torres D et al. Sci Rep, 2017 07;7:4713 Cock-Rada AM et al. Fam Cancer, 2018 01;17:23-30; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620; Wei H et al. Oncol Lett, 2018 Jun;15:9420-9428; Li JY et al. Int J Cancer, 2019 01;144:281-289; Oliver J et al. Front Oncol, 2019 Dec;9:1429). Of note, this alteration has also been reported as 1790delA and 1793delA in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in association with hereditary breast and ovarian cancer (Geisler et al., 2002; Dworkin et al., 2009; Rodriguez et al., 2012; Blay et al., 2013; de Juan Jimenez et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 1793delA; This variant is associated with the following publications: (PMID: 31921681, 11304778, 11773283, 31825140, 34413315, 23683081, 23479189, 9145677, 19340607, 22044689, 16267036, 28024868, 29659587, 28528518, 29752822)
Comment:
This sequence change creates a premature translational stop signal (p.Gly559Valfs*13) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 9145677, 11773283, 23479189, 23683081). This variant is also known as 1790delA and 1793delA. ClinVar contains an entry for this variant (Variation ID: 37425). For these reasons, this variant has been classified as Pathogenic.
Comment:
PM2, PM5_strong, PVS1
Comment:
The BRCA1 p.Gly559Valfs*13 variant was identified in 5 of 5020 proband chromosomes (frequency: 0.001) from individuals or families with non-hereditary diffuse gastric cancer, breast or ovarian cancer and was not identified in 2340 chromosomes from population-matched controls (Blay 2013, Couch 1997, de Juan Jimenez 2013, Sahasrabudhe 2017, Torres 2017). The variant was also identified in dbSNP (ID: rs80357600) as "With Pathogenic allele", ClinVar (classified as pathogenic by Invitae, GeneDx, and nine other submitters), COGR (1x pathogenic), LOVD 3.0 (6x pathogenic), BIC Database (6x with clinical importance), and in ARUP Laboratories database (definitely pathogenic). The variant was not identified in Cosmic, UMD-LSDB, or Zhejiang University databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The c.1674del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 559 and leads to a premature stop codon at position 571. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer (HBOC) syndrome and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
Variant summary: BRCA1 c.1674delA (p.Gly559ValfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250426 control chromosomes (gnomAD). c.1674delA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submissions (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 11773283, 23479189, 23683081, 28680148, 28528518). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been identified in individuals with breast cancer and ovarian cancer in the published literature (PMID: 31921681 (2019), 29446198 (2018), 28680148 (2017), 22044689 (2012), 11773283 (2002), 9145677 (1997)). Based on the available information, this variant is classified as pathogenic.
Comment:
The c.1674delA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 1674, causing a translational frameshift with a predicted alternate stop codon (p.G559Vfs*13). This mutation has been reported in patients with personal and/or family histories suspicious for Hereditary Breast and Ovarian Cancer (Couch FJ et al. N. Engl. J. Med. 1997 May;336:1409-15; Geisler JP et al. J Natl Cancer Inst, 2002 Jan;94:61-7; Shih HA et al. J Clin Oncol, 2002 Feb;20:994-9; Dworkin AM et al. Fam Cancer, 2009 Apr;8:339-46; Rodríguez AO et al. Gynecol Oncol, 2012 Feb;124:236-43; Blay P et al. BMC Cancer. 2013 May;13:243; de Juan Jiménez I et al. Fam Cancer, 2013 Dec;12:767-77; Briceño-Balcázar I et al. Colomb Med (Cali), 2017 Jun;48:58-63; Torres D et al. Sci Rep, 2017 07;7:4713 Cock-Rada AM et al. Fam Cancer, 2018 01;17:23-30; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620; Wei H et al. Oncol Lett, 2018 Jun;15:9420-9428; Li JY et al. Int J Cancer, 2019 01;144:281-289; Oliver J et al. Front Oncol, 2019 Dec;9:1429). Of note, this alteration has also been reported as 1790delA and 1793delA in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in association with hereditary breast and ovarian cancer (Geisler et al., 2002; Dworkin et al., 2009; Rodriguez et al., 2012; Blay et al., 2013; de Juan Jimenez et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 1793delA; This variant is associated with the following publications: (PMID: 31921681, 11304778, 11773283, 31825140, 34413315, 23683081, 23479189, 9145677, 19340607, 22044689, 16267036, 28024868, 29659587, 28528518, 29752822)
Comment:
This sequence change creates a premature translational stop signal (p.Gly559Valfs*13) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 9145677, 11773283, 23479189, 23683081). This variant is also known as 1790delA and 1793delA. ClinVar contains an entry for this variant (Variation ID: 37425). For these reasons, this variant has been classified as Pathogenic.
Comment:
PM2, PM5_strong, PVS1
Comment:
The BRCA1 p.Gly559Valfs*13 variant was identified in 5 of 5020 proband chromosomes (frequency: 0.001) from individuals or families with non-hereditary diffuse gastric cancer, breast or ovarian cancer and was not identified in 2340 chromosomes from population-matched controls (Blay 2013, Couch 1997, de Juan Jimenez 2013, Sahasrabudhe 2017, Torres 2017). The variant was also identified in dbSNP (ID: rs80357600) as "With Pathogenic allele", ClinVar (classified as pathogenic by Invitae, GeneDx, and nine other submitters), COGR (1x pathogenic), LOVD 3.0 (6x pathogenic), BIC Database (6x with clinical importance), and in ARUP Laboratories database (definitely pathogenic). The variant was not identified in Cosmic, UMD-LSDB, or Zhejiang University databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The c.1674del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 559 and leads to a premature stop codon at position 571. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer (HBOC) syndrome and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain). | Pitiot AS | Clinical genetics | 2024 | PMID: 38922859 |
| Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America. | Herzog JS | NPJ breast cancer | 2021 | PMID: 34413315 |
| Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients. | Gao X | Human mutation | 2020 | PMID: 31825140 |
| Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach. | Oliver J | Frontiers in oncology | 2019 | PMID: 31921681 |
| Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer. | Li JY | International journal of cancer | 2019 | PMID: 29752822 |
| Multicenter cross-sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations. | Wei H | Oncology letters | 2018 | PMID: 29805665 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| A multi-gene panel study in hereditary breast and ovarian cancer in Colombia. | Cock-Rada AM | Familial cancer | 2018 | PMID: 28528518 |
| Mutational spectrum in breast cancer associated BRCA1 and BRCA2 genes in Colombia. | Briceño-Balcázar I | Colombia medica (Cali, Colombia) | 2017 | PMID: 29021639 |
| Prevalence and Penetrance of BRCA1 and BRCA2 Germline Mutations in Colombian Breast Cancer Patients. | Torres D | Scientific reports | 2017 | PMID: 28680148 |
| Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer. | Sahasrabudhe R | Gastroenterology | 2017 | PMID: 28024868 |
| Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain). | Blay P | BMC cancer | 2013 | PMID: 23683081 |
| Novel and recurrent BRCA1/BRCA2 mutations in early onset and familial breast and ovarian cancer detected in the Program of Genetic Counseling in Cancer of Valencian Community (eastern Spain). Relationship of family phenotypes with mutation prevalence. | de Juan Jiménez I | Familial cancer | 2013 | PMID: 23479189 |
| BRCA1 and BRCA2 mutations among ovarian cancer patients from Colombia. | Rodríguez AO | Gynecologic oncology | 2012 | PMID: 22044689 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Methylation not a frequent "second hit" in tumors with germline BRCA mutations. | Dworkin AM | Familial cancer | 2009 | PMID: 19340607 |
| BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic. | Shih HA | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2002 | PMID: 11844822 |
| Frequency of BRCA1 dysfunction in ovarian cancer. | Geisler JP | Journal of the National Cancer Institute | 2002 | PMID: 11773283 |
| Germline mutations in BRCA1 and BRCA2 in breast-ovarian families from a breast cancer risk evaluation clinic. | Martin AM | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2001 | PMID: 11304778 |
| BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. | Couch FJ | The New England journal of medicine | 1997 | PMID: 9145677 |
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Text-mined citations for rs80357600 ...
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Record last updated Nov 30, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.