ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8917C>T (p.Arg2973Cys) (rs45469092)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031776 SCV000244489 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000178
Invitae RCV000045657 SCV000073670 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163016 SCV000213504 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Counsyl RCV000031776 SCV000220285 likely benign Breast-ovarian cancer, familial 2 2014-05-01 criteria provided, single submitter literature only
GeneDx RCV000428227 SCV000512394 benign not specified 2015-09-03 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.
Department of Pathology and Molecular Medicine,Queen's University RCV000428227 SCV000588124 benign not specified 2017-04-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000428227 SCV000602818 benign not specified 2016-11-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000428227 SCV000695191 likely benign not specified 2018-05-31 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8917C>T (p.Arg2973Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was observed with an allele frequency of 2.9e-05 in 275120 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (2.9e-05 vs 0.00075), allowing no conclusion about variant significance. The variant, c.8917C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.68_69delAG , p.Glu23fsX17), 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. Multiple ClinVar Submissions from clinical diagnostic laboratories (evaluation after 2014) classify the variant as "likely benign/benign." In addition, multiple publications, Lindor_2012 and Easton_2005, predict the variant to be benign. Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics,PreventionGenetics RCV000034469 SCV000805790 likely benign not provided 2017-08-15 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769706 SCV000901125 likely benign Breast and/or ovarian cancer 2017-09-07 criteria provided, single submitter clinical testing
Color RCV000163016 SCV000910652 benign Hereditary cancer-predisposing syndrome 2016-01-25 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034469 SCV000043235 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000031776 SCV000054384 benign Breast-ovarian cancer, familial 2 2009-11-25 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031776 SCV000147487 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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