Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5558dup (p.Tyr1853Ter)
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
-
NM_007294.4(BRCA1):c.5558dup (p.Tyr1853Ter)
Variation ID: 55628 Accession: VCV000055628.28
- Type and length
-
Duplication, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045711-43045712 (GRCh38) [ NCBI UCSC ] 17: 41197728-41197729 (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.5558dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Tyr1853Ter nonsense NM_001407571.1:c.5345dup NP_001394500.1:p.Tyr1782Terfs frameshift nonsense NM_001407581.1:c.5624dup NP_001394510.1:p.Tyr1875Terfs frameshift nonsense NM_001407582.1:c.5624dup NP_001394511.1:p.Tyr1875Terfs frameshift nonsense NM_001407583.1:c.5621dup NP_001394512.1:p.Tyr1874Terfs frameshift nonsense NM_001407585.1:c.5621dup NP_001394514.1:p.Tyr1874Terfs frameshift nonsense NM_001407587.1:c.5621dup NP_001394516.1:p.Tyr1874Terfs frameshift nonsense NM_001407590.1:c.5618dup NP_001394519.1:p.Tyr1873Terfs frameshift nonsense NM_001407591.1:c.5618dup NP_001394520.1:p.Tyr1873Terfs frameshift nonsense NM_001407593.1:c.5558dup NP_001394522.1:p.Tyr1853Terfs frameshift nonsense NM_001407594.1:c.5558dup NP_001394523.1:p.Tyr1853Terfs frameshift nonsense NM_001407596.1:c.5558dup NP_001394525.1:p.Tyr1853Terfs frameshift nonsense NM_001407597.1:c.5558dup NP_001394526.1:p.Tyr1853Terfs frameshift nonsense NM_001407598.1:c.5558dup NP_001394527.1:p.Tyr1853Terfs frameshift nonsense NM_001407602.1:c.5558dup NP_001394531.1:p.Tyr1853Terfs frameshift nonsense NM_001407603.1:c.5558dup NP_001394532.1:p.Tyr1853Terfs frameshift nonsense NM_001407605.1:c.5558dup NP_001394534.1:p.Tyr1853Terfs frameshift nonsense NM_001407610.1:c.5555dup NP_001394539.1:p.Tyr1852Terfs frameshift nonsense NM_001407611.1:c.5555dup NP_001394540.1:p.Tyr1852Terfs frameshift nonsense NM_001407612.1:c.5555dup NP_001394541.1:p.Tyr1852Terfs frameshift nonsense NM_001407613.1:c.5555dup NP_001394542.1:p.Tyr1852Terfs frameshift nonsense NM_001407614.1:c.5555dup NP_001394543.1:p.Tyr1852Terfs frameshift nonsense NM_001407615.1:c.5555dup NP_001394544.1:p.Tyr1852Terfs frameshift nonsense NM_001407616.1:c.5555dup NP_001394545.1:p.Tyr1852Terfs frameshift nonsense NM_001407617.1:c.5555dup NP_001394546.1:p.Tyr1852Terfs frameshift nonsense NM_001407618.1:c.5555dup NP_001394547.1:p.Tyr1852Terfs frameshift nonsense NM_001407619.1:c.5555dup NP_001394548.1:p.Tyr1852Terfs frameshift nonsense NM_001407620.1:c.5555dup NP_001394549.1:p.Tyr1852Terfs frameshift nonsense NM_001407621.1:c.5555dup NP_001394550.1:p.Tyr1852Terfs frameshift nonsense NM_001407622.1:c.5555dup NP_001394551.1:p.Tyr1852Terfs frameshift nonsense NM_001407623.1:c.5555dup NP_001394552.1:p.Tyr1852Terfs frameshift nonsense NM_001407624.1:c.5555dup NP_001394553.1:p.Tyr1852Terfs frameshift nonsense NM_001407625.1:c.5555dup NP_001394554.1:p.Tyr1852Terfs frameshift nonsense NM_001407626.1:c.5555dup NP_001394555.1:p.Tyr1852Terfs frameshift nonsense NM_001407627.1:c.5552dup NP_001394556.1:p.Tyr1851Terfs frameshift nonsense NM_001407628.1:c.5552dup NP_001394557.1:p.Tyr1851Terfs frameshift nonsense NM_001407629.1:c.5552dup NP_001394558.1:p.Tyr1851Terfs frameshift nonsense NM_001407630.1:c.5552dup NP_001394559.1:p.Tyr1851Terfs frameshift nonsense NM_001407631.1:c.5552dup NP_001394560.1:p.Tyr1851Terfs frameshift nonsense NM_001407632.1:c.5552dup NP_001394561.1:p.Tyr1851Terfs frameshift nonsense NM_001407633.1:c.5552dup NP_001394562.1:p.Tyr1851Terfs frameshift nonsense NM_001407634.1:c.5552dup NP_001394563.1:p.Tyr1851Terfs frameshift nonsense NM_001407635.1:c.5552dup NP_001394564.1:p.Tyr1851Terfs frameshift nonsense NM_001407636.1:c.5552dup NP_001394565.1:p.Tyr1851Terfs frameshift nonsense NM_001407637.1:c.5552dup NP_001394566.1:p.Tyr1851Terfs frameshift nonsense NM_001407638.1:c.5552dup NP_001394567.1:p.Tyr1851Terfs frameshift nonsense NM_001407639.1:c.5552dup NP_001394568.1:p.Tyr1851Terfs frameshift nonsense NM_001407640.1:c.5552dup NP_001394569.1:p.Tyr1851Terfs frameshift nonsense NM_001407641.1:c.5552dup NP_001394570.1:p.Tyr1851Terfs frameshift nonsense NM_001407642.1:c.5552dup NP_001394571.1:p.Tyr1851Terfs frameshift nonsense NM_001407644.1:c.5549dup NP_001394573.1:p.Tyr1850Terfs frameshift nonsense NM_001407645.1:c.5549dup NP_001394574.1:p.Tyr1850Terfs frameshift nonsense NM_001407646.1:c.5546dup NP_001394575.1:p.Tyr1849Terfs frameshift nonsense NM_001407647.1:c.5543dup NP_001394576.1:p.Tyr1848Terfs frameshift nonsense NM_001407648.1:c.5501dup NP_001394577.1:p.Tyr1834Terfs frameshift nonsense NM_001407649.1:c.5498dup NP_001394578.1:p.Tyr1833Terfs frameshift nonsense NM_001407652.1:c.5480dup NP_001394581.1:p.Tyr1827Terfs frameshift nonsense NM_001407653.1:c.5480dup NP_001394582.1:p.Tyr1827Terfs frameshift nonsense NM_001407654.1:c.5480dup NP_001394583.1:p.Tyr1827Terfs frameshift nonsense NM_001407655.1:c.5480dup NP_001394584.1:p.Tyr1827Terfs frameshift nonsense NM_001407656.1:c.5477dup NP_001394585.1:p.Tyr1826Terfs frameshift nonsense NM_001407657.1:c.5477dup NP_001394586.1:p.Tyr1826Terfs frameshift nonsense NM_001407658.1:c.5477dup NP_001394587.1:p.Tyr1826Terfs frameshift nonsense NM_001407659.1:c.5474dup NP_001394588.1:p.Tyr1825Terfs frameshift nonsense NM_001407660.1:c.5474dup NP_001394589.1:p.Tyr1825Terfs frameshift nonsense NM_001407661.1:c.5474dup NP_001394590.1:p.Tyr1825Terfs frameshift nonsense NM_001407662.1:c.5474dup NP_001394591.1:p.Tyr1825Terfs frameshift nonsense NM_001407663.1:c.5474dup NP_001394592.1:p.Tyr1825Terfs frameshift nonsense NM_001407664.1:c.5435dup NP_001394593.1:p.Tyr1812Terfs frameshift nonsense NM_001407665.1:c.5435dup NP_001394594.1:p.Tyr1812Terfs frameshift nonsense NM_001407666.1:c.5435dup NP_001394595.1:p.Tyr1812Terfs frameshift nonsense NM_001407667.1:c.5435dup NP_001394596.1:p.Tyr1812Terfs frameshift nonsense NM_001407668.1:c.5435dup NP_001394597.1:p.Tyr1812Terfs frameshift nonsense NM_001407669.1:c.5435dup NP_001394598.1:p.Tyr1812Terfs frameshift nonsense NM_001407670.1:c.5432dup NP_001394599.1:p.Tyr1811Terfs frameshift nonsense NM_001407671.1:c.5432dup NP_001394600.1:p.Tyr1811Terfs frameshift nonsense NM_001407672.1:c.5432dup NP_001394601.1:p.Tyr1811Terfs frameshift nonsense NM_001407673.1:c.5432dup NP_001394602.1:p.Tyr1811Terfs frameshift nonsense NM_001407674.1:c.5432dup NP_001394603.1:p.Tyr1811Terfs frameshift nonsense NM_001407675.1:c.5432dup NP_001394604.1:p.Tyr1811Terfs frameshift nonsense NM_001407676.1:c.5432dup NP_001394605.1:p.Tyr1811Terfs frameshift nonsense NM_001407677.1:c.5432dup NP_001394606.1:p.Tyr1811Terfs frameshift nonsense NM_001407678.1:c.5432dup NP_001394607.1:p.Tyr1811Terfs frameshift nonsense NM_001407679.1:c.5432dup NP_001394608.1:p.Tyr1811Terfs frameshift nonsense NM_001407680.1:c.5432dup NP_001394609.1:p.Tyr1811Terfs frameshift nonsense NM_001407681.1:c.5429dup NP_001394610.1:p.Tyr1810Terfs frameshift nonsense NM_001407682.1:c.5429dup NP_001394611.1:p.Tyr1810Terfs frameshift nonsense NM_001407683.1:c.5429dup NP_001394612.1:p.Tyr1810Terfs frameshift nonsense NM_001407684.1:c.5429dup NP_001394613.1:p.Tyr1810Terfs frameshift nonsense NM_001407685.1:c.5429dup NP_001394614.1:p.Tyr1810Terfs frameshift nonsense NM_001407686.1:c.5429dup NP_001394615.1:p.Tyr1810Terfs frameshift nonsense NM_001407687.1:c.5429dup NP_001394616.1:p.Tyr1810Terfs frameshift nonsense NM_001407688.1:c.5429dup NP_001394617.1:p.Tyr1810Terfs frameshift nonsense NM_001407689.1:c.5429dup NP_001394618.1:p.Tyr1810Terfs frameshift nonsense NM_001407690.1:c.5426dup NP_001394619.1:p.Tyr1809Terfs frameshift nonsense NM_001407691.1:c.5426dup NP_001394620.1:p.Tyr1809Terfs frameshift nonsense NM_001407692.1:c.5417dup NP_001394621.1:p.Tyr1806Terfs frameshift nonsense NM_001407694.1:c.5417dup NP_001394623.1:p.Tyr1806Terfs frameshift nonsense NM_001407695.1:c.5417dup NP_001394624.1:p.Tyr1806Terfs frameshift nonsense NM_001407696.1:c.5417dup NP_001394625.1:p.Tyr1806Terfs frameshift nonsense NM_001407697.1:c.5417dup NP_001394626.1:p.Tyr1806Terfs frameshift nonsense NM_001407698.1:c.5417dup NP_001394627.1:p.Tyr1806Terfs frameshift nonsense NM_001407724.1:c.5417dup NP_001394653.1:p.Tyr1806Terfs frameshift nonsense NM_001407725.1:c.5417dup NP_001394654.1:p.Tyr1806Terfs frameshift nonsense NM_001407726.1:c.5417dup NP_001394655.1:p.Tyr1806Terfs frameshift nonsense NM_001407727.1:c.5417dup NP_001394656.1:p.Tyr1806Terfs frameshift nonsense NM_001407728.1:c.5417dup NP_001394657.1:p.Tyr1806Terfs frameshift nonsense NM_001407729.1:c.5417dup NP_001394658.1:p.Tyr1806Terfs frameshift nonsense NM_001407730.1:c.5417dup NP_001394659.1:p.Tyr1806Terfs frameshift nonsense NM_001407731.1:c.5417dup NP_001394660.1:p.Tyr1806Terfs frameshift nonsense NM_001407732.1:c.5414dup NP_001394661.1:p.Tyr1805Terfs frameshift nonsense NM_001407733.1:c.5414dup NP_001394662.1:p.Tyr1805Terfs frameshift nonsense NM_001407734.1:c.5414dup NP_001394663.1:p.Tyr1805Terfs frameshift nonsense NM_001407735.1:c.5414dup NP_001394664.1:p.Tyr1805Terfs frameshift nonsense NM_001407736.1:c.5414dup NP_001394665.1:p.Tyr1805Terfs frameshift nonsense NM_001407737.1:c.5414dup NP_001394666.1:p.Tyr1805Terfs frameshift nonsense NM_001407738.1:c.5414dup NP_001394667.1:p.Tyr1805Terfs frameshift nonsense NM_001407739.1:c.5414dup NP_001394668.1:p.Tyr1805Terfs frameshift nonsense NM_001407740.1:c.5414dup NP_001394669.1:p.Tyr1805Terfs frameshift nonsense NM_001407741.1:c.5414dup NP_001394670.1:p.Tyr1805Terfs frameshift nonsense NM_001407742.1:c.5414dup NP_001394671.1:p.Tyr1805Terfs frameshift nonsense NM_001407743.1:c.5414dup NP_001394672.1:p.Tyr1805Terfs frameshift nonsense NM_001407744.1:c.5414dup NP_001394673.1:p.Tyr1805Terfs frameshift nonsense NM_001407745.1:c.5414dup NP_001394674.1:p.Tyr1805Terfs frameshift nonsense NM_001407746.1:c.5414dup NP_001394675.1:p.Tyr1805Terfs frameshift nonsense NM_001407747.1:c.5414dup NP_001394676.1:p.Tyr1805Terfs frameshift nonsense NM_001407748.1:c.5414dup NP_001394677.1:p.Tyr1805Terfs frameshift nonsense NM_001407749.1:c.5414dup NP_001394678.1:p.Tyr1805Terfs frameshift nonsense NM_001407750.1:c.5414dup NP_001394679.1:p.Tyr1805Terfs frameshift nonsense NM_001407751.1:c.5414dup NP_001394680.1:p.Tyr1805Terfs frameshift nonsense NM_001407752.1:c.5414dup NP_001394681.1:p.Tyr1805Terfs frameshift nonsense NM_001407838.1:c.5411dup NP_001394767.1:p.Tyr1804Terfs frameshift nonsense NM_001407839.1:c.5411dup NP_001394768.1:p.Tyr1804Terfs frameshift nonsense NM_001407841.1:c.5411dup NP_001394770.1:p.Tyr1804Terfs frameshift nonsense NM_001407842.1:c.5411dup NP_001394771.1:p.Tyr1804Terfs frameshift nonsense NM_001407843.1:c.5411dup NP_001394772.1:p.Tyr1804Terfs frameshift nonsense NM_001407844.1:c.5411dup NP_001394773.1:p.Tyr1804Terfs frameshift nonsense NM_001407845.1:c.5411dup NP_001394774.1:p.Tyr1804Terfs frameshift nonsense NM_001407846.1:c.5411dup NP_001394775.1:p.Tyr1804Terfs frameshift nonsense NM_001407847.1:c.5411dup NP_001394776.1:p.Tyr1804Terfs frameshift nonsense NM_001407848.1:c.5411dup NP_001394777.1:p.Tyr1804Terfs frameshift nonsense NM_001407849.1:c.5411dup NP_001394778.1:p.Tyr1804Terfs frameshift nonsense NM_001407850.1:c.5411dup NP_001394779.1:p.Tyr1804Terfs frameshift nonsense NM_001407851.1:c.5411dup NP_001394780.1:p.Tyr1804Terfs frameshift nonsense NM_001407852.1:c.5411dup NP_001394781.1:p.Tyr1804Terfs frameshift nonsense NM_001407853.1:c.5411dup NP_001394782.1:p.Tyr1804Terfs frameshift nonsense NM_001407854.1:c.*72dup NM_001407858.1:c.*72dup NM_001407859.1:c.*72dup NM_001407860.1:c.*72dup NM_001407861.1:c.*72dup NM_001407862.1:c.5357dup NP_001394791.1:p.Tyr1786Terfs frameshift nonsense NM_001407863.1:c.5354dup NP_001394792.1:p.Tyr1785Terfs frameshift nonsense NM_001407874.1:c.5351dup NP_001394803.1:p.Tyr1784Terfs frameshift nonsense NM_001407875.1:c.5351dup NP_001394804.1:p.Tyr1784Terfs frameshift nonsense NM_001407879.1:c.5348dup NP_001394808.1:p.Tyr1783Terfs frameshift nonsense NM_001407881.1:c.5348dup NP_001394810.1:p.Tyr1783Terfs frameshift nonsense NM_001407882.1:c.5348dup NP_001394811.1:p.Tyr1783Terfs frameshift nonsense NM_001407884.1:c.5348dup NP_001394813.1:p.Tyr1783Terfs frameshift nonsense NM_001407885.1:c.5348dup NP_001394814.1:p.Tyr1783Terfs frameshift nonsense NM_001407886.1:c.5348dup NP_001394815.1:p.Tyr1783Terfs frameshift nonsense NM_001407887.1:c.5348dup NP_001394816.1:p.Tyr1783Terfs frameshift nonsense NM_001407889.1:c.5348dup NP_001394818.1:p.Tyr1783Terfs frameshift nonsense NM_001407894.1:c.5345dup NP_001394823.1:p.Tyr1782Terfs frameshift nonsense NM_001407895.1:c.5345dup NP_001394824.1:p.Tyr1782Terfs frameshift nonsense NM_001407896.1:c.5345dup NP_001394825.1:p.Tyr1782Terfs frameshift nonsense NM_001407897.1:c.5345dup NP_001394826.1:p.Tyr1782Terfs frameshift nonsense NM_001407898.1:c.5345dup NP_001394827.1:p.Tyr1782Terfs frameshift nonsense NM_001407899.1:c.5345dup NP_001394828.1:p.Tyr1782Terfs frameshift nonsense NM_001407900.1:c.5345dup NP_001394829.1:p.Tyr1782Terfs frameshift nonsense NM_001407902.1:c.5345dup NP_001394831.1:p.Tyr1782Terfs frameshift nonsense NM_001407904.1:c.5345dup NP_001394833.1:p.Tyr1782Terfs frameshift nonsense NM_001407906.1:c.5345dup NP_001394835.1:p.Tyr1782Terfs frameshift nonsense NM_001407907.1:c.5345dup NP_001394836.1:p.Tyr1782Terfs frameshift nonsense NM_001407908.1:c.5345dup NP_001394837.1:p.Tyr1782Terfs frameshift nonsense NM_001407909.1:c.5345dup NP_001394838.1:p.Tyr1782Terfs frameshift nonsense NM_001407910.1:c.5345dup NP_001394839.1:p.Tyr1782Terfs frameshift nonsense NM_001407915.1:c.5342dup NP_001394844.1:p.Tyr1781Terfs frameshift nonsense NM_001407916.1:c.5342dup NP_001394845.1:p.Tyr1781Terfs frameshift nonsense NM_001407917.1:c.5342dup NP_001394846.1:p.Tyr1781Terfs frameshift nonsense NM_001407918.1:c.5342dup NP_001394847.1:p.Tyr1781Terfs frameshift nonsense NM_001407919.1:c.5306dup NP_001394848.1:p.Tyr1769Terfs frameshift nonsense NM_001407920.1:c.5294dup NP_001394849.1:p.Tyr1765Terfs frameshift nonsense NM_001407921.1:c.5294dup NP_001394850.1:p.Tyr1765Terfs frameshift nonsense NM_001407922.1:c.5294dup NP_001394851.1:p.Tyr1765Terfs frameshift nonsense NM_001407923.1:c.5294dup NP_001394852.1:p.Tyr1765Terfs frameshift nonsense NM_001407924.1:c.5294dup NP_001394853.1:p.Tyr1765Terfs frameshift nonsense NM_001407925.1:c.5294dup NP_001394854.1:p.Tyr1765Terfs frameshift nonsense NM_001407926.1:c.5294dup NP_001394855.1:p.Tyr1765Terfs frameshift nonsense NM_001407927.1:c.5291dup NP_001394856.1:p.Tyr1764Terfs frameshift nonsense NM_001407928.1:c.5291dup NP_001394857.1:p.Tyr1764Terfs frameshift nonsense NM_001407929.1:c.5291dup NP_001394858.1:p.Tyr1764Terfs frameshift nonsense NM_001407930.1:c.5291dup NP_001394859.1:p.Tyr1764Terfs frameshift nonsense NM_001407931.1:c.5291dup NP_001394860.1:p.Tyr1764Terfs frameshift nonsense NM_001407932.1:c.5291dup NP_001394861.1:p.Tyr1764Terfs frameshift nonsense NM_001407933.1:c.5291dup NP_001394862.1:p.Tyr1764Terfs frameshift nonsense NM_001407934.1:c.5288dup NP_001394863.1:p.Tyr1763Terfs frameshift nonsense NM_001407935.1:c.5288dup NP_001394864.1:p.Tyr1763Terfs frameshift nonsense NM_001407936.1:c.5288dup NP_001394865.1:p.Tyr1763Terfs frameshift nonsense NM_001407937.1:c.*72dup NM_001407938.1:c.*72dup NM_001407939.1:c.*72dup NM_001407940.1:c.*72dup NM_001407941.1:c.*72dup NM_001407942.1:c.*72dup NM_001407943.1:c.*72dup NM_001407944.1:c.*72dup NM_001407945.1:c.*72dup NM_001407946.1:c.5225dup NP_001394875.1:p.Tyr1742Terfs frameshift nonsense NM_001407947.1:c.5225dup NP_001394876.1:p.Tyr1742Terfs frameshift nonsense NM_001407948.1:c.5225dup NP_001394877.1:p.Tyr1742Terfs frameshift nonsense NM_001407949.1:c.5225dup NP_001394878.1:p.Tyr1742Terfs frameshift nonsense NM_001407950.1:c.5222dup NP_001394879.1:p.Tyr1741Terfs frameshift nonsense NM_001407951.1:c.5222dup NP_001394880.1:p.Tyr1741Terfs frameshift nonsense NM_001407952.1:c.5222dup NP_001394881.1:p.Tyr1741Terfs frameshift nonsense NM_001407953.1:c.5222dup NP_001394882.1:p.Tyr1741Terfs frameshift nonsense NM_001407954.1:c.5222dup NP_001394883.1:p.Tyr1741Terfs frameshift nonsense NM_001407955.1:c.5222dup NP_001394884.1:p.Tyr1741Terfs frameshift nonsense NM_001407956.1:c.5219dup NP_001394885.1:p.Tyr1740Terfs frameshift nonsense NM_001407957.1:c.5219dup NP_001394886.1:p.Tyr1740Terfs frameshift nonsense NM_001407958.1:c.5219dup NP_001394887.1:p.Tyr1740Terfs frameshift nonsense NM_001407959.1:c.5177dup NP_001394888.1:p.Tyr1726Terfs frameshift nonsense NM_001407960.1:c.5174dup NP_001394889.1:p.Tyr1725Terfs frameshift nonsense NM_001407962.1:c.5174dup NP_001394891.1:p.Tyr1725Terfs frameshift nonsense NM_001407963.1:c.5171dup NP_001394892.1:p.Tyr1724Terfs frameshift nonsense NM_001407964.1:c.5096dup NP_001394893.1:p.Tyr1699Terfs frameshift nonsense NM_001407965.1:c.5051dup NP_001394894.1:p.Tyr1684Terfs frameshift nonsense NM_001407966.1:c.4670dup NP_001394895.1:p.Tyr1557Terfs frameshift nonsense NM_001407967.1:c.4667dup NP_001394896.1:p.Tyr1556Terfs frameshift nonsense NM_001407968.1:c.2954dup NP_001394897.1:p.Tyr985Terfs frameshift nonsense NM_001407969.1:c.2951dup NP_001394898.1:p.Tyr984Terfs frameshift nonsense NM_001407970.1:c.2315dup NP_001394899.1:p.Tyr772Terfs frameshift nonsense NM_001407971.1:c.2315dup NP_001394900.1:p.Tyr772Terfs frameshift nonsense NM_001407972.1:c.2312dup NP_001394901.1:p.Tyr771Terfs frameshift nonsense NM_001407973.1:c.2249dup NP_001394902.1:p.Tyr750Terfs frameshift nonsense NM_001407974.1:c.2249dup NP_001394903.1:p.Tyr750Terfs frameshift nonsense NM_001407975.1:c.2249dup NP_001394904.1:p.Tyr750Terfs frameshift nonsense NM_001407976.1:c.2249dup NP_001394905.1:p.Tyr750Terfs frameshift nonsense NM_001407977.1:c.2249dup NP_001394906.1:p.Tyr750Terfs frameshift nonsense NM_001407978.1:c.2249dup NP_001394907.1:p.Tyr750Terfs frameshift nonsense NM_001407979.1:c.2246dup NP_001394908.1:p.Tyr749Terfs frameshift nonsense NM_001407980.1:c.2246dup NP_001394909.1:p.Tyr749Terfs frameshift nonsense NM_001407981.1:c.2246dup NP_001394910.1:p.Tyr749Terfs frameshift nonsense NM_001407982.1:c.2246dup NP_001394911.1:p.Tyr749Terfs frameshift nonsense NM_001407983.1:c.2246dup NP_001394912.1:p.Tyr749Terfs frameshift nonsense NM_001407984.1:c.2246dup NP_001394913.1:p.Tyr749Terfs frameshift nonsense NM_001407985.1:c.2246dup NP_001394914.1:p.Tyr749Terfs frameshift nonsense NM_001407986.1:c.2246dup NP_001394915.1:p.Tyr749Terfs frameshift nonsense NM_001407990.1:c.2246dup NP_001394919.1:p.Tyr749Terfs frameshift nonsense NM_001407991.1:c.2246dup NP_001394920.1:p.Tyr749Terfs frameshift nonsense NM_001407992.1:c.2246dup NP_001394921.1:p.Tyr749Terfs frameshift nonsense NM_001407993.1:c.2246dup NP_001394922.1:p.Tyr749Terfs frameshift nonsense NM_001408392.1:c.2243dup NP_001395321.1:p.Tyr748Terfs frameshift nonsense NM_001408396.1:c.2243dup NP_001395325.1:p.Tyr748Terfs frameshift nonsense NM_001408397.1:c.2243dup NP_001395326.1:p.Tyr748Terfs frameshift nonsense NM_001408398.1:c.2243dup NP_001395327.1:p.Tyr748Terfs frameshift nonsense NM_001408399.1:c.2243dup NP_001395328.1:p.Tyr748Terfs frameshift nonsense NM_001408400.1:c.2243dup NP_001395329.1:p.Tyr748Terfs frameshift nonsense NM_001408401.1:c.2243dup NP_001395330.1:p.Tyr748Terfs frameshift nonsense NM_001408402.1:c.2243dup NP_001395331.1:p.Tyr748Terfs frameshift nonsense NM_001408403.1:c.2243dup NP_001395332.1:p.Tyr748Terfs frameshift nonsense NM_001408404.1:c.2243dup NP_001395333.1:p.Tyr748Terfs frameshift nonsense NM_001408406.1:c.2240dup NP_001395335.1:p.Tyr747Terfs frameshift nonsense NM_001408407.1:c.2240dup NP_001395336.1:p.Tyr747Terfs frameshift nonsense NM_001408408.1:c.2240dup NP_001395337.1:p.Tyr747Terfs frameshift nonsense NM_001408409.1:c.2237dup NP_001395338.1:p.Tyr746Terfs frameshift nonsense NM_001408410.1:c.2174dup NP_001395339.1:p.Tyr725Terfs frameshift nonsense NM_001408411.1:c.2171dup NP_001395340.1:p.Tyr724Terfs frameshift nonsense NM_001408412.1:c.2168dup NP_001395341.1:p.Tyr723Terfs frameshift nonsense NM_001408413.1:c.2168dup NP_001395342.1:p.Tyr723Terfs frameshift nonsense NM_001408414.1:c.2168dup NP_001395343.1:p.Tyr723Terfs frameshift nonsense NM_001408415.1:c.2168dup NP_001395344.1:p.Tyr723Terfs frameshift nonsense NM_001408416.1:c.2168dup NP_001395345.1:p.Tyr723Terfs frameshift nonsense NM_001408418.1:c.2132dup NP_001395347.1:p.Tyr711Terfs frameshift nonsense NM_001408419.1:c.2132dup NP_001395348.1:p.Tyr711Terfs frameshift nonsense NM_001408420.1:c.2132dup NP_001395349.1:p.Tyr711Terfs frameshift nonsense NM_001408421.1:c.2129dup NP_001395350.1:p.Tyr710Terfs frameshift nonsense NM_001408422.1:c.2129dup NP_001395351.1:p.Tyr710Terfs frameshift nonsense NM_001408423.1:c.2129dup NP_001395352.1:p.Tyr710Terfs frameshift nonsense NM_001408424.1:c.2129dup NP_001395353.1:p.Tyr710Terfs frameshift nonsense NM_001408425.1:c.2126dup NP_001395354.1:p.Tyr709Terfs frameshift nonsense NM_001408426.1:c.2126dup NP_001395355.1:p.Tyr709Terfs frameshift nonsense NM_001408427.1:c.2126dup NP_001395356.1:p.Tyr709Terfs frameshift nonsense NM_001408428.1:c.2126dup NP_001395357.1:p.Tyr709Terfs frameshift nonsense NM_001408429.1:c.2126dup NP_001395358.1:p.Tyr709Terfs frameshift nonsense NM_001408430.1:c.2126dup NP_001395359.1:p.Tyr709Terfs frameshift nonsense NM_001408431.1:c.2126dup NP_001395360.1:p.Tyr709Terfs frameshift nonsense NM_001408432.1:c.2123dup NP_001395361.1:p.Tyr708Terfs frameshift nonsense NM_001408433.1:c.2123dup NP_001395362.1:p.Tyr708Terfs frameshift nonsense NM_001408434.1:c.2123dup NP_001395363.1:p.Tyr708Terfs frameshift nonsense NM_001408435.1:c.2123dup NP_001395364.1:p.Tyr708Terfs frameshift nonsense NM_001408436.1:c.2123dup NP_001395365.1:p.Tyr708Terfs frameshift nonsense NM_001408437.1:c.2123dup NP_001395366.1:p.Tyr708Terfs frameshift nonsense NM_001408438.1:c.2123dup NP_001395367.1:p.Tyr708Terfs frameshift nonsense NM_001408439.1:c.2123dup NP_001395368.1:p.Tyr708Terfs frameshift nonsense NM_001408440.1:c.2123dup NP_001395369.1:p.Tyr708Terfs frameshift nonsense NM_001408441.1:c.2123dup NP_001395370.1:p.Tyr708Terfs frameshift nonsense NM_001408442.1:c.2123dup NP_001395371.1:p.Tyr708Terfs frameshift nonsense NM_001408443.1:c.2123dup NP_001395372.1:p.Tyr708Terfs frameshift nonsense NM_001408444.1:c.2123dup NP_001395373.1:p.Tyr708Terfs frameshift nonsense NM_001408445.1:c.2120dup NP_001395374.1:p.Tyr707Terfs frameshift nonsense NM_001408446.1:c.2120dup NP_001395375.1:p.Tyr707Terfs frameshift nonsense NM_001408447.1:c.2120dup NP_001395376.1:p.Tyr707Terfs frameshift nonsense NM_001408448.1:c.2120dup NP_001395377.1:p.Tyr707Terfs frameshift nonsense NM_001408450.1:c.2120dup NP_001395379.1:p.Tyr707Terfs frameshift nonsense NM_001408451.1:c.2114dup NP_001395380.1:p.Tyr705Terfs frameshift nonsense NM_001408452.1:c.2108dup NP_001395381.1:p.Tyr703Terfs frameshift nonsense NM_001408453.1:c.2108dup NP_001395382.1:p.Tyr703Terfs frameshift nonsense NM_001408454.1:c.2108dup NP_001395383.1:p.Tyr703Terfs frameshift nonsense NM_001408455.1:c.2108dup NP_001395384.1:p.Tyr703Terfs frameshift nonsense NM_001408456.1:c.2108dup NP_001395385.1:p.Tyr703Terfs frameshift nonsense NM_001408457.1:c.2108dup NP_001395386.1:p.Tyr703Terfs frameshift nonsense NM_001408458.1:c.2105dup NP_001395387.1:p.Tyr702Terfs frameshift nonsense NM_001408459.1:c.2105dup NP_001395388.1:p.Tyr702Terfs frameshift nonsense NM_001408460.1:c.2105dup NP_001395389.1:p.Tyr702Terfs frameshift nonsense NM_001408461.1:c.2105dup NP_001395390.1:p.Tyr702Terfs frameshift nonsense NM_001408462.1:c.2105dup NP_001395391.1:p.Tyr702Terfs frameshift nonsense NM_001408463.1:c.2105dup NP_001395392.1:p.Tyr702Terfs frameshift nonsense NM_001408464.1:c.2105dup NP_001395393.1:p.Tyr702Terfs frameshift nonsense NM_001408465.1:c.2105dup NP_001395394.1:p.Tyr702Terfs frameshift nonsense NM_001408466.1:c.2105dup NP_001395395.1:p.Tyr702Terfs frameshift nonsense NM_001408467.1:c.2105dup NP_001395396.1:p.Tyr702Terfs frameshift nonsense NM_001408468.1:c.2102dup NP_001395397.1:p.Tyr701Terfs frameshift nonsense NM_001408469.1:c.2102dup NP_001395398.1:p.Tyr701Terfs frameshift nonsense NM_001408470.1:c.2102dup NP_001395399.1:p.Tyr701Terfs frameshift nonsense NM_001408472.1:c.*72dup NM_001408473.1:c.*72dup NM_001408474.1:c.2048dup NP_001395403.1:p.Tyr683Terfs frameshift nonsense NM_001408475.1:c.2045dup NP_001395404.1:p.Tyr682Terfs frameshift nonsense NM_001408476.1:c.2045dup NP_001395405.1:p.Tyr682Terfs frameshift nonsense NM_001408478.1:c.2039dup NP_001395407.1:p.Tyr680Terfs frameshift nonsense NM_001408479.1:c.2039dup NP_001395408.1:p.Tyr680Terfs frameshift nonsense NM_001408480.1:c.2039dup NP_001395409.1:p.Tyr680Terfs frameshift nonsense NM_001408481.1:c.2036dup NP_001395410.1:p.Tyr679Terfs frameshift nonsense NM_001408482.1:c.2036dup NP_001395411.1:p.Tyr679Terfs frameshift nonsense NM_001408483.1:c.2036dup NP_001395412.1:p.Tyr679Terfs frameshift nonsense NM_001408484.1:c.2036dup NP_001395413.1:p.Tyr679Terfs frameshift nonsense NM_001408485.1:c.2036dup NP_001395414.1:p.Tyr679Terfs frameshift nonsense NM_001408489.1:c.2036dup NP_001395418.1:p.Tyr679Terfs frameshift nonsense NM_001408490.1:c.2036dup NP_001395419.1:p.Tyr679Terfs frameshift nonsense NM_001408491.1:c.2036dup NP_001395420.1:p.Tyr679Terfs frameshift nonsense NM_001408492.1:c.2033dup NP_001395421.1:p.Tyr678Terfs frameshift nonsense NM_001408493.1:c.2033dup NP_001395422.1:p.Tyr678Terfs frameshift nonsense NM_001408494.1:c.2009dup NP_001395423.1:p.Tyr670Terfs frameshift nonsense NM_001408495.1:c.2003dup NP_001395424.1:p.Tyr668Terfs frameshift nonsense NM_001408496.1:c.1985dup NP_001395425.1:p.Tyr662Terfs frameshift nonsense NM_001408497.1:c.1985dup NP_001395426.1:p.Tyr662Terfs frameshift nonsense NM_001408498.1:c.1985dup NP_001395427.1:p.Tyr662Terfs frameshift nonsense NM_001408499.1:c.1985dup NP_001395428.1:p.Tyr662Terfs frameshift nonsense NM_001408500.1:c.1985dup NP_001395429.1:p.Tyr662Terfs frameshift nonsense NM_001408501.1:c.1985dup NP_001395430.1:p.Tyr662Terfs frameshift nonsense NM_001408502.1:c.1982dup NP_001395431.1:p.Tyr661Terfs frameshift nonsense NM_001408503.1:c.1982dup NP_001395432.1:p.Tyr661Terfs frameshift nonsense NM_001408504.1:c.1982dup NP_001395433.1:p.Tyr661Terfs frameshift nonsense NM_001408505.1:c.1979dup NP_001395434.1:p.Tyr660Terfs frameshift nonsense NM_001408506.1:c.1922dup NP_001395435.1:p.Tyr641Terfs frameshift nonsense NM_001408507.1:c.1919dup NP_001395436.1:p.Tyr640Terfs frameshift nonsense NM_001408508.1:c.1910dup NP_001395437.1:p.Tyr637Terfs frameshift nonsense NM_001408509.1:c.1907dup NP_001395438.1:p.Tyr636Terfs frameshift nonsense NM_001408510.1:c.1868dup NP_001395439.1:p.Tyr623Terfs frameshift nonsense NM_001408511.1:c.1865dup NP_001395440.1:p.Tyr622Terfs frameshift nonsense NM_001408512.1:c.1745dup NP_001395441.1:p.Tyr582Terfs frameshift nonsense NM_001408513.1:c.1718dup NP_001395442.1:p.Tyr573Terfs frameshift nonsense NM_001408514.1:c.1322dup NP_001395443.1:p.Tyr441Terfs frameshift nonsense NM_007294.3:c.5558dupA frameshift nonsense NM_007297.4:c.5417dup NP_009228.2:p.Tyr1806Ter nonsense NM_007298.4:c.2246dup NP_009229.2:p.Tyr749Terfs frameshift nonsense NM_007299.4:c.*72dup 3 prime UTR NM_007300.4:c.5621dup NP_009231.2:p.Tyr1874Ter nonsense NM_007304.2:c.2246dup NP_009235.2:p.Tyr749Terfs frameshift nonsense NR_027676.2:n.5735dup non-coding transcript variant NC_000017.11:g.43045712dup NC_000017.10:g.41197729dup NG_005905.2:g.172272dup LRG_292:g.172272dup U14680.1:c.5558_5559insA U14680.1:n.5677_5678insA - Protein change
- Y1853*, Y1806*, Y1874*, Y749*
- Other names
-
p.Tyr1853*
5677insA
- Canonical SPDI
- NC_000017.11:43045711:T:TT
-
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.
-
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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 (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 17, 2024 | RCV000049050.23 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 4, 2021 | RCV000163976.18 | |
| Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Jul 31, 2023 | RCV000265181.18 | |
| Pathogenic (6) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000074357.23 |
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. |
|
|---|---|---|---|---|---|
|
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: SCV000300281.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Apr 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001572495.1
First in ClinVar: Apr 30, 2021 Last updated: Apr 30, 2021 |
Comment:
Variant summary: BRCA1 c.5558dupA (p.Tyr1853X) results in a premature termination codon, predicted to cause a truncation of the encoded protein The variant was absent in … (more)
Variant summary: BRCA1 c.5558dupA (p.Tyr1853X) results in a premature termination codon, predicted to cause a truncation of the encoded protein The variant was absent in 253430 control chromosomes (gnomAD). c.5558dupA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer Syndrome (example: Song_2014, Judkins_2005) and also has been found to co-segregate within a large affected family (Friedman_1994). These data indicate that the variant is very likely to be associated with disease. In functional studies, the variant has been found to reduce transcriptional activity (Carvalho_2007). Eight ClinVar submitters (evaluation after 2014) including an expert panel (ENIGMA) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Sep 07, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888951.2
First in ClinVar: Dec 19, 2017 Last updated: Jan 03, 2022 |
|
|
|
Pathogenic
(Jan 15, 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: SCV000904687.3
First in ClinVar: May 19, 2019 Last updated: Jan 15, 2022 |
Comment:
This variant is located in the BRCA1 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. This variant has not … (more)
This variant is located in the BRCA1 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jan 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004216850.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
|
Pathogenic
(May 25, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449857.1
First in ClinVar: Dec 10, 2020 Last updated: Dec 10, 2020 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Apr 07, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000488476.2
First in ClinVar: Sep 24, 2016 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Oct 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000329130.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency … (more)
Nonsense variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; 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 5677dupA; This variant is associated with the following publications: (PMID: 21922593, 20104584, 7894493, 8942979, 14534301, 7795652, 27802165, 10811118, 12400015, 28392550, 25186627, 24728189, 18992264, 31013702, 24504028, 30787465, 30765603, 34439109, Levine[case report], 32322110, 33237286) (less)
|
|
|
Pathogenic
(Nov 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003809834.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 17, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000077063.12
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1853*) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Tyr1853*) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the BRCA1 protein. 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: 7894493, 20104584, 24504028). It has also been observed to segregate with disease in related individuals. This variant is also known as (c.5677insA, Y1853_L1854delinsX). ClinVar contains an entry for this variant (Variation ID: 55628). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects BRCA1 function (PMID: 10811118, 11739404, 12400015, 21922593). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000214576.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The c.5558dupA pathogenic mutation, located in coding exon 22 of the BRCA1 gene, results from a duplication of A at nucleotide position 5558, causing a … (more)
The c.5558dupA pathogenic mutation, located in coding exon 22 of the BRCA1 gene, results from a duplication of A at nucleotide position 5558, causing a translational frameshift with a predicted alternate stop codon (p.Y1853*). This alteration occurs at the 3' terminus of theBRCA1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 11 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This mutation has been identified in multiple individuals with Hereditary Breast and Ovarian Cancer (HBOC) syndrome (Friedman et al. Nat. Genet. 1994 Dec;8(4):399-404; Borg et al. Hum. Mutat. 2010 Mar;31(3):E1200-40; Song H et al. Hum. Mol. Genet. 2014 Sep;23(17):4703-9; Tung N et al. Cancer, 2015 Jan;121:25-33), and has been shown to cause loss of function in functional assays (Hayes et al. Cancer Res. 2000 May;60(9):2411-8). Of note, this alteration is also designated as 5677insA in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jul 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV005413221.1
First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024 |
Comment:
PP4, PP5, PM2_moderate, PS4_moderate, PVS1_strong
Number of individuals with the variant: 1
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Pathogenic
(May 01, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000053867.6
First in ClinVar: Apr 04, 2013 Last updated: Oct 11, 2015 |
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587522.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Pathogenic
(Dec 01, 1994)
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no assertion criteria provided
Method: literature only
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BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000039536.4
First in ClinVar: Apr 04, 2013 Last updated: May 09, 2018 |
Comment on evidence:
Friedman et al. (1994) studied 63 breast cancer patients and 10 ovarian cancer patients in 10 families with cancer linked to chromosome 17q21 (604370). They … (more)
Friedman et al. (1994) studied 63 breast cancer patients and 10 ovarian cancer patients in 10 families with cancer linked to chromosome 17q21 (604370). They identified a 1-bp (A) insertion at nucleotide 5677 in exon 24 of the BRCA1 gene, leading to a premature termination codon in place of tyrosine-1853 and a truncated protein. (less)
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145577.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 4
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 3:
Number of individuals with the variant: 7
Ethnicity/Population group: Western European
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Comment:
Comment:
Variant summary: BRCA1 c.5558dupA (p.Tyr1853X) results in a premature termination codon, predicted to cause a truncation of the encoded protein The variant was absent in 253430 control chromosomes (gnomAD). c.5558dupA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer Syndrome (example: Song_2014, Judkins_2005) and also has been found to co-segregate within a large affected family (Friedman_1994). These data indicate that the variant is very likely to be associated with disease. In functional studies, the variant has been found to reduce transcriptional activity (Carvalho_2007). Eight ClinVar submitters (evaluation after 2014) including an expert panel (ENIGMA) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant is located in the BRCA1 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; 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 5677dupA; This variant is associated with the following publications: (PMID: 21922593, 20104584, 7894493, 8942979, 14534301, 7795652, 27802165, 10811118, 12400015, 28392550, 25186627, 24728189, 18992264, 31013702, 24504028, 30787465, 30765603, 34439109, Levine[case report], 32322110, 33237286)
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1853*) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the BRCA1 protein. 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: 7894493, 20104584, 24504028). It has also been observed to segregate with disease in related individuals. This variant is also known as (c.5677insA, Y1853_L1854delinsX). ClinVar contains an entry for this variant (Variation ID: 55628). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects BRCA1 function (PMID: 10811118, 11739404, 12400015, 21922593). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.5558dupA pathogenic mutation, located in coding exon 22 of the BRCA1 gene, results from a duplication of A at nucleotide position 5558, causing a translational frameshift with a predicted alternate stop codon (p.Y1853*). This alteration occurs at the 3' terminus of theBRCA1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 11 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This mutation has been identified in multiple individuals with Hereditary Breast and Ovarian Cancer (HBOC) syndrome (Friedman et al. Nat. Genet. 1994 Dec;8(4):399-404; Borg et al. Hum. Mutat. 2010 Mar;31(3):E1200-40; Song H et al. Hum. Mol. Genet. 2014 Sep;23(17):4703-9; Tung N et al. Cancer, 2015 Jan;121:25-33), and has been shown to cause loss of function in functional assays (Hayes et al. Cancer Res. 2000 May;60(9):2411-8). Of note, this alteration is also designated as 5677insA in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
PP4, PP5, PM2_moderate, PS4_moderate, PVS1_strong
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.5558dupA (p.Tyr1853X) results in a premature termination codon, predicted to cause a truncation of the encoded protein The variant was absent in 253430 control chromosomes (gnomAD). c.5558dupA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer Syndrome (example: Song_2014, Judkins_2005) and also has been found to co-segregate within a large affected family (Friedman_1994). These data indicate that the variant is very likely to be associated with disease. In functional studies, the variant has been found to reduce transcriptional activity (Carvalho_2007). Eight ClinVar submitters (evaluation after 2014) including an expert panel (ENIGMA) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant is located in the BRCA1 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; 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 5677dupA; This variant is associated with the following publications: (PMID: 21922593, 20104584, 7894493, 8942979, 14534301, 7795652, 27802165, 10811118, 12400015, 28392550, 25186627, 24728189, 18992264, 31013702, 24504028, 30787465, 30765603, 34439109, Levine[case report], 32322110, 33237286)
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1853*) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the BRCA1 protein. 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: 7894493, 20104584, 24504028). It has also been observed to segregate with disease in related individuals. This variant is also known as (c.5677insA, Y1853_L1854delinsX). ClinVar contains an entry for this variant (Variation ID: 55628). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects BRCA1 function (PMID: 10811118, 11739404, 12400015, 21922593). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.5558dupA pathogenic mutation, located in coding exon 22 of the BRCA1 gene, results from a duplication of A at nucleotide position 5558, causing a translational frameshift with a predicted alternate stop codon (p.Y1853*). This alteration occurs at the 3' terminus of theBRCA1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 11 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This mutation has been identified in multiple individuals with Hereditary Breast and Ovarian Cancer (HBOC) syndrome (Friedman et al. Nat. Genet. 1994 Dec;8(4):399-404; Borg et al. Hum. Mutat. 2010 Mar;31(3):E1200-40; Song H et al. Hum. Mol. Genet. 2014 Sep;23(17):4703-9; Tung N et al. Cancer, 2015 Jan;121:25-33), and has been shown to cause loss of function in functional assays (Hayes et al. Cancer Res. 2000 May;60(9):2411-8). Of note, this alteration is also designated as 5677insA in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
PP4, PP5, PM2_moderate, PS4_moderate, PVS1_strong
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. | Tung N | Cancer | 2015 | PMID: 25186627 |
| The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. | Song H | Human molecular genetics | 2014 | PMID: 24728189 |
| Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. | Cunningham JM | Scientific reports | 2014 | PMID: 24504028 |
| Assessment of human Nter and Cter BRCA1 mutations using growth and localization assays in yeast. | Millot GA | Human mutation | 2011 | PMID: 21922593 |
| 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 |
| Analysis of a set of missense, frameshift, and in-frame deletion variants of BRCA1. | Carvalho M | Mutation research | 2009 | PMID: 18992264 |
| Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis. | Carvalho MA | Cancer research | 2007 | PMID: 17308087 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
| Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells. | Kawai H | Oncogene | 2002 | PMID: 12400015 |
| BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations. | Ye Q | The Journal of cell biology | 2001 | PMID: 11739404 |
| Functional assay for BRCA1: mutagenesis of the COOH-terminal region reveals critical residues for transcription activation. | Hayes F | Cancer research | 2000 | PMID: 10811118 |
| The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression. | Yu X | The Journal of biological chemistry | 1998 | PMID: 9738006 |
| Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families. | Friedman LS | Nature genetics | 1994 | PMID: 7894493 |
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Text-mined citations for rs80357629 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
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.