ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5170A>G (p.Ile1724Val) (rs35335654)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131376 SCV000186352 likely benign Hereditary cancer-predisposing syndrome 2019-03-20 criteria provided, single submitter clinical testing Other data supporting benign classification;In silico models in agreement (benign)
GeneDx RCV000160227 SCV000210611 likely benign not specified 2017-12-04 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.
Invitae RCV000206856 SCV000260001 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000160227 SCV000694834 likely benign not specified 2020-07-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5170A>G (p.Ile1724Val) results in a conservative amino acid change in 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 4.5e-05 in 242492 control chromosomes, predominantly at a frequency of 0.00071 within the African or African-American 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 (4.5e-05 vs 0.00075), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.5170A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported in the literature. Co-occurrences with other pathogenic variants have been reported in BRCA patient databases (BRCA1 c.211A>G , p.Arg71Gly and BRCA1 c.470_471delCT , p.Ser157X in UMD database; BRCA1 943ins10 in BIC), providing supporting evidence for a benign role. Six other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587993 SCV000887843 likely benign not provided 2019-07-04 criteria provided, single submitter clinical testing
Color RCV000131376 SCV000903441 benign Hereditary cancer-predisposing syndrome 2015-11-16 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082938 SCV000115012 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000082938 SCV000146556 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
3DMed Clinical Laboratory Inc RCV000677857 SCV000804018 likely benign Ovarian cancer 2018-01-02 no assertion criteria provided clinical testing

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