ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5170A>G (p.Ile1724Val)

gnomAD frequency: 0.00023  dbSNP: rs35335654
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Total submissions: 12
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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 This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000587993 SCV000210611 likely benign not provided 2020-10-23 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25348012)
Labcorp Genetics (formerly Invitae), Labcorp RCV000206856 SCV000260001 likely benign Hereditary breast ovarian cancer syndrome 2024-01-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160227 SCV000694834 benign not specified 2021-09-10 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. In addition, this variant was found in 5/2559 African individuals over age 70 with no history of cancer. 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. Co-occurrences with other pathogenic variants have been reported (BRCA1 c.211A>G , p.Arg71Gly; BRCA1 c.470_471delCT , p.Ser157X; BRCA1 943ins10), providing supporting evidence for a benign role. Six 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 benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587993 SCV000887843 likely benign not provided 2021-01-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000131376 SCV000903441 benign Hereditary cancer-predisposing syndrome 2015-11-16 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000160227 SCV002065240 likely benign not specified 2021-04-29 criteria provided, single submitter clinical testing
Mendelics RCV000131376 SCV004814098 likely benign Hereditary cancer-predisposing syndrome 2024-04-08 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082938 SCV000115012 benign Breast-ovarian cancer, familial, susceptibility to, 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000082938 SCV000146556 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 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
PreventionGenetics, part of Exact Sciences RCV004529872 SCV004753149 likely benign BRCA2-related disorder 2022-03-24 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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