ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9190G>A (p.Asp3064Asn) (rs80359177)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001083475 SCV000073755 likely benign Hereditary breast and ovarian cancer syndrome 2020-10-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130150 SCV000184984 likely benign Hereditary cancer-predisposing syndrome 2018-10-26 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
GeneDx RCV000440778 SCV000517839 likely benign not specified 2017-06-07 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 RCV000440778 SCV000695216 likely benign not specified 2020-10-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9190G>A (p.Asp3064Asn) results in a conservative amino acid change located in the BRCA2, OB3 domain (IPR015188) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251296 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9190G>A has been reported in the literature in patients undergoing testing without information on cancer phenotype and in the UK10K cohort of control individuals collected as part of non-cancer studies (example, Qian_2018, Pritchard_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Furthermore, a computational method that produces a probabilistic likelihood ratio has reported this variant as having a neutral outcome (Karchin_2008). At-least one co-occurrence with another pathogenic variant has been reported at our laboratory (BRCA2 c.6408_6414delAAATGTT, p.N2137fs*29), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation reporting a majority consensus towards a benign/likely benign outcome (n=5). Some submitters cite overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was re-classified as likely benign.
Counsyl RCV000077462 SCV000786192 uncertain significance Breast-ovarian cancer, familial 2 2018-03-21 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130150 SCV000911250 benign Hereditary cancer-predisposing syndrome 2016-12-19 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077462 SCV000109260 benign Breast-ovarian cancer, familial 2 2012-03-20 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077462 SCV000147562 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000590167 SCV000778723 uncertain significance not provided 2015-10-07 no assertion criteria provided clinical testing
True Health Diagnostics RCV000130150 SCV000886677 likely benign Hereditary cancer-predisposing syndrome 2018-08-07 no assertion criteria provided clinical testing

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