ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8918G>A (p.Arg2973His) (rs80359143)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082957 SCV000073671 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000128971 SCV000172856 likely benign Hereditary cancer-predisposing syndrome 2019-04-28 criteria provided, single submitter clinical testing In silico models in agreement (benign);Intact protein function observed in appropriate functional assay(s);Other data supporting benign classification
GeneDx RCV000587937 SCV000210676 likely benign not provided 2020-02-04 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 29884841, 31131967, 30212499, 16284991, 22034289, 19043619, 22711857, 21702907, 20127978, 30287823)
Color Health, Inc RCV000128971 SCV000537482 likely benign Hereditary cancer-predisposing syndrome 2014-11-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000505714 SCV000695192 likely benign not specified 2021-03-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8918G>A (p.Arg2973His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 249436 control chromosomes. This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (4e-05 vs 0.00075), allowing no conclusion about variant significance. c.8918G>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Alsop_2012, Fackenthal_2012, Pal_2005). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A Japanese case-control study reported the variant as "benign" due to its presence in controls and absence in cases (Momozawa_2018). One co-occurrence with another pathogenic variant has been reported (BRCA2 c.1219_1219delC, p.Gln407Argfs, BIC), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant on HDR activity (Hart_2019). Seven ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=3) and likely benign (n=4). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587937 SCV000887947 likely benign not provided 2019-02-20 criteria provided, single submitter clinical testing
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000761134 SCV000891050 uncertain significance Neuroblastoma 2017-04-03 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770734 SCV000902215 uncertain significance Breast and/or ovarian cancer 2016-12-08 criteria provided, single submitter clinical testing
Mendelics RCV000031777 SCV001139238 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642495 SCV001852819 likely benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031777 SCV000054385 likely benign Breast-ovarian cancer, familial 2 2013-11-05 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031777 SCV000147488 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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