ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3785C>G (p.Ser1262Ter) (rs80358620)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129108 SCV000183819 pathogenic Hereditary cancer-predisposing syndrome 2017-11-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA2) RCV000113219 SCV000146297 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113219 SCV000326915 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000113219 SCV000786273 pathogenic Breast-ovarian cancer, familial 2 2018-04-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113219 SCV000282383 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000481804 SCV000566129 pathogenic not provided 2018-11-26 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3785C>G at the cDNA level and p.Ser1262Ter (S1262X) at the protein level. Using alternate nomenclature, this variant would be defined as 4013C>G. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with breast and ovarian cancer (Loughrey 2008, de Juan Jim?nez 2013, Song 2014). We consider this variant to be pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000113219 SCV000993559 pathogenic Breast-ovarian cancer, familial 2 2019-05-23 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000044266 SCV000916867 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-29 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3785C>G (p.Ser1262X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Val1283fsX2 and p.Lys1289fsX3). The variant allele was found at a frequency of 8.4e-06 in 118690 control chromosomes. c.3785C>G has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000044266 SCV000072279 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1262*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80358620, ExAC 0.002%). This particular variant has been reported in the literature in an individual affected with ovarian cancer (PMID: 24728189). ClinVar contains an entry for this variant (Variation ID: 51525). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000113219 SCV000297522 pathogenic Breast-ovarian cancer, familial 2 2012-04-30 no assertion criteria provided clinical testing
True Health Diagnostics RCV000129108 SCV000805241 pathogenic Hereditary cancer-predisposing syndrome 2018-04-09 no assertion criteria provided clinical testing

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