ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8972G>A (p.Arg2991His) (rs80359150)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001086948 SCV000073689 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131351 SCV000186326 likely benign Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing Other data supporting benign classification;Other strong data supporting benign classification
GeneDx RCV000435349 SCV000518105 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000435349 SCV000695198 likely benign not specified 2020-07-30 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8972G>A (p.Arg2991His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.4e-05 in 250784 control chromosomes, predominantly at a frequency of 0.00041 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer Syndrome (8.4e-05 vs 0.00075), allowing no conclusion about variant significance. c.8972G>A has been reported in the literature in at least one individual at risk of Breast and Ovarian Cancer (Zuntini_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variants have been reported (BRCA2 c.5645C>A, p.Ser1882X; BRCA2 c.9924C>G, p.Tyr3308Ter), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function (Whiley_2010, Guidugli_2018). These results showed no damaging effect of this variant. Five other ClinVar submitters (evaluation after 2014) cite the variant as likely benign/benign (n=4) or VUS (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000761071 SCV000890986 uncertain significance Retinoblastoma 2016-05-11 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131351 SCV000910894 likely benign Hereditary cancer-predisposing syndrome 2015-10-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000435349 SCV001470464 benign not specified 2020-01-24 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031783 SCV000054391 benign Breast-ovarian cancer, familial 2 2012-01-05 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031783 SCV000147505 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.