ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5909C>A (p.Ser1970Ter) (rs80358824)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131108 SCV000186038 pathogenic Hereditary cancer-predisposing syndrome 2017-08-30 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) RCV000031588 SCV000146729 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131108 SCV000683741 pathogenic Hereditary cancer-predisposing syndrome 2017-01-17 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031588 SCV000327307 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031588 SCV000786116 pathogenic Breast-ovarian cancer, familial 2 2018-02-27 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000257911 SCV000592013 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000257911 SCV000588106 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Division Human Genetics,Medical University Innsbruck RCV000031588 SCV000212023 pathogenic Breast-ovarian cancer, familial 2 2015-02-11 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031588 SCV000282417 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735577 SCV000863715 pathogenic Breast and/or ovarian cancer no assertion criteria provided clinical testing
GeneDx RCV000255943 SCV000321471 pathogenic not provided 2018-09-24 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.5909C>A at the cDNA level and p.Ser1970Ter (S1970X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also published as BRCA2 6137C>A, has been reported in association with hereditary breast, ovarian, and prostate cancer (Gayther 1997, Shih 2002, Al-Mulla 2009, Leongamornlert 2014, Song 2014, Maxwell 2016) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000257911 SCV000694916 pathogenic Hereditary breast and ovarian cancer syndrome 2016-03-28 criteria provided, single submitter clinical testing Variant summary: The variant of interest causes a nonsense mutation in exon 11 resulting in a premature termination codon, a known mechanism for disease, as these types of variants are predicted to cause transcript degradation through nonsense mediated decay or produce a truncated protein. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Lys2013X, p.Ser2378X, p.Arg2494X, etc.). The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP), and has been reported in multiple affected individuals via publications. In addition, multiple reputable databases/clinical laboraotories cite the variant with a classification of "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
Invitae RCV000257911 SCV000072804 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1970*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with prostate cancer (PMID: 20736950, 24556621), breast cancer (PMID: 27469594, 25682074), ovarian cancer (PMID: 8988179, 24728189), and individuals from families with hereditary breast and ovarian cancer (PMID: 21120943, 27225819). This variant is also known as 6137C>A in the literature (PMID: 8988179). ClinVar contains an entry for this variant (Variation ID: 38007). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000255943 SCV000296535 pathogenic not provided 2016-04-23 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000257911 SCV000587810 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031588 SCV000054194 pathogenic Breast-ovarian cancer, familial 2 2012-01-10 no assertion criteria provided clinical testing

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