ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9242T>C (p.Val3081Ala) (rs80359189)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203623 SCV000073768 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129976 SCV000184800 likely benign Hereditary cancer-predisposing syndrome 2018-10-08 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);Other data supporting benign classification
GeneDx RCV000045755 SCV000210682 likely benign not specified 2017-08-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Health, Inc RCV000129976 SCV000684041 likely benign Hereditary cancer-predisposing syndrome 2016-04-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000045755 SCV000695221 likely benign not specified 2020-07-10 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9242T>C (p.Val3081Ala) results in a non-conservative amino acid change located in the OB3 fold (IPR015188) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 347936 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. Though the variant, c.9242T>C, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer Syndrome and related tumor phenotypes, it was also found in several healthy controls (Grant_2015, Shimelis_2017, Zuntini_2018, Al Hannan_2019). Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.8364G>A, p.Trp2788X; in UMD), providing supporting evidence for a benign role. An in vitro functional study reported that this variant results in an activity comparable to the wild type in homology-directed DNA repair (HDR) assays (Guidugli_2018, Hart_2018). In addition, a recent multifactorial likelihood analysis predicted this variant to be Likely Benign (Parsons_2019). Five other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as Likely benign (4x) or VUS (1x). Based on the evidence outlined above, the variant was classified as likely benign.
Mendelics RCV000203623 SCV000838899 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000031805 SCV001139251 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284113 SCV001469727 uncertain significance not provided 2020-07-24 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031805 SCV000054413 likely benign Breast-ovarian cancer, familial 2 2012-03-27 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031805 SCV000147576 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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