ClinVar Genomic variation as it relates to human health
NM_024675.4(PALB2):c.3549C>A (p.Tyr1183Ter)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_024675.4(PALB2):c.3549C>A (p.Tyr1183Ter)
Variation ID: 128144 Accession: VCV000128144.45
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p12.2 16: 23603471 (GRCh38) [ NCBI UCSC ] 16: 23614792 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jan 31, 2016 Jun 17, 2024 Apr 5, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024675.4:c.3549C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_078951.2:p.Tyr1183Ter nonsense NC_000016.10:g.23603471G>T NC_000016.9:g.23614792G>T NG_007406.1:g.42887C>A LRG_308:g.42887C>A LRG_308t1:c.3549C>A LRG_308p1:p.Tyr1183Ter - Protein change
- Y1183*
- Other names
- p.Y1183*:TAC>TAA
- NM_024675.4(PALB2):c.3549C>A
- p.Tyr1183Ter
- Canonical SPDI
- NC_000016.10:23603470:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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 | ||
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HI score
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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. |
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PALB2 | - | - |
GRCh38 GRCh37 |
5899 | 5940 |
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. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Dec 14, 2022 | RCV000116108.24 | |
Pathogenic (6) |
reviewed by expert panel
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Apr 5, 2023 | RCV000200012.26 | |
Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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Mar 17, 2022 | RCV000212831.31 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 5, 2019 | RCV000587765.10 | |
Pathogenic (2) |
criteria provided, single submitter
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Feb 15, 2022 | RCV000763376.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 28, 2023 | RCV003493446.1 | |
PALB2-related disorder
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Pathogenic (1) |
criteria provided, single submitter
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Feb 26, 2024 | RCV004528809.1 |
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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Pathogenic
(Apr 05, 2023)
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reviewed by expert panel
Method: curation
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen
FDA Recognized Database
Accession: SCV003915570.1 First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
Comment:
The c.3549C>A (p.Tyr1183Ter) variant in PALB2 is a nonsense variant that may cause a premature stop codon that is predicted to escape nonsense mediated decay, … (more)
The c.3549C>A (p.Tyr1183Ter) variant in PALB2 is a nonsense variant that may cause a premature stop codon that is predicted to escape nonsense mediated decay, however it is a truncation of a functionally important region (removes amino acids 1183-1186) in a gene where loss-of-function is an established disease mechanism. This variant, or another variant leading to the same protein truncation, has been detected in three individuals with autosomal recessive FANCN. Of those individuals, three were compound heterozygous for the variant and a pathogenic or likely pathogenic variant and three of those were confirmed in trans by parental testing (co-occurring variants: c.2257C>T (p.Arg753Ter); c.2962C>T (p.Gln988Ter); c.3116delA (p.Asn1039Ilefs*2): PMID 17200671). The variant has been reported to segregate with breast and/or pancreatic cancer in 15 affected members from 6 families (Invitae; Ambry Genetics). This variant is non-functional in multiple different protein assays (PMID 31757951, PMID 31636395); however due to a lack of positive missense controls with known clinical impact, these protein assays do not meet the requirements for use by the HBOP VCEP. In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant hereditary breast and pancreatic cancer and autosomal recessive FANCN based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP. (PVS1, PP1_Strong, PM3_Strong) (less)
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Pathogenic
(Feb 01, 2018)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884280.1
First in ClinVar: Sep 28, 2017 Last updated: Sep 28, 2017 |
Comment:
The PALB2 c.3549C>A; p.Tyr1183Ter variant (rs118203998) is described in individuals and families affected with breast cancer, ovarian cancer and pancreatic cancer; and in Fanconi anemia … (more)
The PALB2 c.3549C>A; p.Tyr1183Ter variant (rs118203998) is described in individuals and families affected with breast cancer, ovarian cancer and pancreatic cancer; and in Fanconi anemia when paired with another pathogenic variant on the opposite chromosome (Hoffstatter 2011, Reid 2007, Susswein 2016). This variant removes four amino acids thought to be critical in the protein structure, which may destabilize the protein (Oliver 2009). In support of this theory, cells derived from individuals harboring this variant and another truncation variant on the opposite chromosome do not produce PALB2 protein (Reid 2007). The variant is listed in the ClinVar database (Variation ID: 128144). The variant is also listed in the Genome Aggregation Database in 1 out of 246208 alleles. Considering available information, this variant is classified as pathogenic. Pathogenic PALB2 variants increase susceptibility to breast and pancreatic cancer (OMIM#601355). References: Hofstatter EW et al. PALB2 mutations in familial breast and pancreatic cancer. Fam Cancer. 2011 Jun;10(2):225-31. Oliver AW et al. Structural basis for recruitment of BRCA2 by PALB2. EMBO Rep. 2009 Sep;10(9):990-6. Reid S et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet. 2007 Feb;39(2):162-4. Susswein LR et al. Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Genet Med. 2016 Aug;18(8):823-32. (less)
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Pathogenic
(Nov 05, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699600.2
First in ClinVar: Mar 17, 2018 Last updated: Jun 22, 2020 |
Comment:
Variant summary: PALB2 c.3549C>A (p.Tyr1183X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: PALB2 c.3549C>A (p.Tyr1183X) 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. The variant allele was found at a frequency of 3.9e-06 in 258634 control chromosomes. c.3549C>A has been well reported in the literature in multiple individuals affected with several cancer phenotypes such as, epithelial ovarian cancer (Ramus_2015), in bi allelic PALB2 mediated Fanconi anemia (with p.R753*, Reid_2007), breast and pancreatic cancer (Hofstatter_2011), and male breast cancer (Ding_2011). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in no detectable PALB2 protein in lymphoblastoid cells of a patient with the Fanconi anemia phenotype, thereby confirming the null allele outcome for this variant (Reid_2007). Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Mar 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002051617.2
First in ClinVar: Jan 08, 2022 Last updated: Feb 12, 2022 |
Comment:
PS3, PS4, PM2, PM3
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Pathogenic
(Nov 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
maternal
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004175940.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
Criteria applied: PVS1, PS1_MOD, PM2_SUP
Clinical Features:
Family history of cancer (present)
Sex: female
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Pathogenic
(Dec 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
maternal
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004242407.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
Criteria applied: PVS1,PS1,PS4
Clinical Features:
Family history of cancer (present)
Sex: female
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Pathogenic
(Dec 14, 2022)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV000537656.4
First in ClinVar: Mar 24, 2017 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 13 of the PALB2 gene, creating a premature translation stop signal. Functional studies have shown that the PALB2 … (more)
This variant changes 1 nucleotide in exon 13 of the PALB2 gene, creating a premature translation stop signal. Functional studies have shown that the PALB2 protein is not detectable in a carrier of this variant (PMID: 17200671) and is predicted to disrupt the BRCA2/RAD51 binding domain (PMID: 19609323). This variant has been reported in over ten individuals affected with breast or ovarian cancer (PMID: 20927582, 25099575, 26296701, 26315354, 26681312, 26641009). This variant (c.3549C>A) and a different nucleotide change resulting in the same protein consequence (c.3549C>G) have been observed in three individuals diagnosed with Fanconi anemia who also carried different pathogenic variants in the same gene (PMID: 17200671). This variant has been identified in 1/251420 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 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 28, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV003836276.2
First in ClinVar: Mar 11, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Fanconi anemia complementation group N Pancreatic cancer, susceptibility to, 3
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000894073.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Feb 15, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Fanconi anemia complementation group N Pancreatic cancer, susceptibility to, 3
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000611292.2
First in ClinVar: Nov 11, 2017 Last updated: Dec 31, 2022 |
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Pathogenic
(Mar 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000150017.17
First in ClinVar: May 17, 2014 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; Reported in multiple individuals with … (more)
Nonsense variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Reported in multiple individuals with PALB2-related cancers (Rahman 2007, Ding 2011, Hofstatter 2011, Antoniou 2014, Ellingson 2015, Ramus 2015).; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26296701, 19763819, 26596371, 27356891, 21618343, 21365267, 20927582, 28873162, 19584259, 17200671, 25225577, 18053174, 21153565, 18302019, 23935381, 19609323, 17200668, 21165770, 26315354, 19464302, 24998779, 25099575, 26681312, 26641009, 24728327, 28008555, 29387807, 28152038, 26283626, 19264984, 29785153, 31948886, 32546565, 31589614, 33403473, 33882707, 33420229) (less)
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Pathogenic
(Mar 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004019625.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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Pathogenic
(Feb 27, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601789.5
First in ClinVar: Sep 28, 2017 Last updated: Jan 06, 2024 |
Comment:
This nonsense variant causes the premature termination of PALB2 protein synthesis. In the published literature, this variant has been reported in individuals with breast, ovarian … (more)
This nonsense variant causes the premature termination of PALB2 protein synthesis. In the published literature, this variant has been reported in individuals with breast, ovarian and pancreatic cancer in the published literature (PMID: 26681312 (2015), 26315354 (2015), 26296701 (2015), 25099575 (2014), 21365267 (2011), 19264984 (2009)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 14, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000253944.12
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1183*) in the PALB2 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Tyr1183*) in the PALB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acid(s) of the PALB2 protein. This variant is present in population databases (rs118203998, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with breast cancer and Fanconi anemia (PMID: 17200671, 20927582, 21165770, 21365267, 26283626, 26296701). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 128144). 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 PALB2 function (PMID: 17200671, 19609323, 31757951). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Feb 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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PALB2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004109519.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
The PALB2 c.3549C>A variant is predicted to result in premature protein termination (p.Tyr1183*). This variant has been reported in multiple individuals with breast, ovarian, or … (more)
The PALB2 c.3549C>A variant is predicted to result in premature protein termination (p.Tyr1183*). This variant has been reported in multiple individuals with breast, ovarian, or pancreatic cancer (Churpek et al. 2015. PubMed ID: 26641009; Hofstatter et al. 2011. PubMed ID: 21365267; Table S1, Susswein et al. 2015. PubMed ID: 26681312). This variant removes the last four c-terminal amino acids from the protein and is thought to contribute to protein destabilization (Oliver et al. 2009. PubMed ID: 19609323). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD and has been interpreted by multiple laboratories as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/128144/). Nonsense variants in PALB2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Mar 17, 2022)
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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: SCV000172793.10
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.Y1183* pathogenic mutation (also known as c.3549C>A), located in coding exon 13 of the PALB2 gene, results from a C to A substitution at … (more)
The p.Y1183* pathogenic mutation (also known as c.3549C>A), located in coding exon 13 of the PALB2 gene, results from a C to A substitution at nucleotide position 3549. This changes the amino acid from a tyrosine to a stop codon within exon 13. This alteration occurs at the 3' terminus of PALB2 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last four 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). The p.Y1183* mutation has been identified with a PALB2 pathogenic variant in multiple individuals with clinical features of Fanconi Anemia-N (FA-N) (Reid S et al. Nat. Genet. 2007 Feb;39:162-4). Lymphoblastoid cells from at least one of these patients was found to have no detectable PALB2 protein (Reid S et al. Nat. Genet. 2007 Feb;39:162-4). Truncations at this position have been reported in multiple familial breast cancer kindreds to date (Rahman N et al. Nat. Genet. 2007 Feb;39:165-7; Hofstatter EW et al. Fam. Cancer. 2011 Jun;10:225-31; Tischkowitz M et al. Hum. Mutat. 2012 Apr;33:674-80). This alteration was also identified in 4/10030 consecutive breast cancer patients referred for evaluation by an NGS hereditary cancer panel (Susswein LR et al. Genet. Med. 2016 Aug;18:823-32). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jun 05, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002531190.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The PALB2 c.3549C>A (p.Y1183X) variant has been reported in heterozygosity in at least 6 individuals with breast cancer (PMID: 26681312, 21365267, 26296701). One individual also … (more)
The PALB2 c.3549C>A (p.Y1183X) variant has been reported in heterozygosity in at least 6 individuals with breast cancer (PMID: 26681312, 21365267, 26296701). One individual also had pancreatic cancer and the variant segregated in a relative with pancreatic cancer (PMID 21365267). Pathogenic variants in PALB2 also cause autosomal recessive Fanconi anemia. This variant has been detected in compound heterozygosity in at least 1 individual with Fanconi Anemia (PMID: 17200671). Based on the genomic location of the variant, this variant is not predicted to cause nonsense-mediated decay but the protein product is expected to be truncated. However immunoblot from patient cells showed an absence of PALB2 protein (PMID 17200671). This variant was observed in 1/113726 chromosomes in the Non-Finnish European population, according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 128144). A different nucleotide change resulting in the same amino acid change, c.3549C>G (p.Y1183X), has been reported in individuals affected with breast, ovarian, or pancreatic cancer (PMID: 26681312, 29360161, 31159747, 32339256) as well as compound heterozygous and homozygous individuals with Fanconi Anemia (PMID 32461654). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
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Pathogenic
(Sep 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000489276.2
First in ClinVar: Jan 31, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001980152.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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Pathogenic
(May 13, 2019)
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no assertion criteria provided
Method: curation
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not provided
Affected status: yes
Allele origin:
germline
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Leiden Open Variation Database
Accession: SCV001193429.1
First in ClinVar: Apr 06, 2020 Last updated: Apr 06, 2020 |
Comment:
Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, LOVD-team, but with Curator vacancy, Marc Tischkowitz.
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743808.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927276.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954340.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing. | Zhou J | Cancer | 2020 | PMID: 32339256 |
Functional analysis of genetic variants in the high-risk breast cancer susceptibility gene PALB2. | Boonen RACM | Nature communications | 2019 | PMID: 31757951 |
Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. | Tsaousis GN | BMC cancer | 2019 | PMID: 31159747 |
Germline mutation prevalence in individuals with pancreatic cancer and a history of previous malignancy. | Dudley B | Cancer | 2018 | PMID: 29360161 |
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia. | Churpek JE | Cancer | 2016 | PMID: 26641009 |
Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer. | Ramus SJ | Journal of the National Cancer Institute | 2015 | PMID: 26315354 |
Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy. | Ellingson MS | Breast cancer research and treatment | 2015 | PMID: 26296701 |
Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls. | Thompson ER | Breast cancer research : BCR | 2015 | PMID: 26283626 |
Breast-cancer risk in families with mutations in PALB2. | Antoniou AC | The New England journal of medicine | 2014 | PMID: 25099575 |
PALB2 mutations in familial breast and pancreatic cancer. | Hofstatter EW | Familial cancer | 2011 | PMID: 21365267 |
PALB2 mutations in German and Russian patients with bilateral breast cancer. | Bogdanova N | Breast cancer research and treatment | 2011 | PMID: 21165770 |
Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. | Ding YC | Breast cancer research and treatment | 2011 | PMID: 20927582 |
Structural basis for recruitment of BRCA2 by PALB2. | Oliver AW | EMBO reports | 2009 | PMID: 19609323 |
PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2. | Zhang F | Molecular cancer research : MCR | 2009 | PMID: 19584259 |
Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. | Jones S | Science (New York, N.Y.) | 2009 | PMID: 19264984 |
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. | Reid S | Nature genetics | 2007 | PMID: 17200671 |
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. | Rahman N | Nature genetics | 2007 | PMID: 17200668 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d4d23a6e-70c6-488d-99e5-a88d9f38ae15 | - | - | - | - |
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Text-mined citations for rs118203998 ...
HelpRecord last updated Sep 08, 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.