ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5536A>G (p.Ile1846Val) (rs587782375)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131366 SCV000186342 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000588246 SCV000694877 uncertain significance not provided 2016-09-09 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5536A>G (p.Ile1846Val) variant located in a BRCA2 repeat domain causes a missense change involving a conserved nucleotide with 3/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a "benign" outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 14/120826 (1/8628), predominantly in the South Asian cohort, 14/16408 (1/1172), which slightly exceeds the maximum expected allele frequency for a pathogenic BRCA2 variant of 1/1333. Therefore, suggesting the variant could possible be a benign polymorphism found in population(s) of South Asian origin. The variant of interest has been reported in an affected individual via a publication. However, multiple reputable clinical diagnostic laboratories cite the variant as "uncertain significance," with one citing the variant as "likely benign," with no additional information for an independent evaluation. Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Invitae RCV000233290 SCV000283264 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-11 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000210966 SCV000267782 uncertain significance Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506172 SCV000600645 uncertain significance not specified 2017-05-30 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000210966 SCV000297538 uncertain significance Breast-ovarian cancer, familial 2 2010-06-02 no assertion criteria provided clinical testing

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