ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2464T>C (p.Cys822Arg) (rs80358512)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044001 SCV000072014 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 822 of the BRCA2 protein (p.Cys822Arg). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with hereditary breast and ovarian cancer (PMID: 28477318). ClinVar contains an entry for this variant (Variation ID: 51292). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000220861 SCV000273411 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000220861 SCV000688759 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-26 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780041 SCV000917056 uncertain significance not specified 2018-12-03 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.2464T>C (p.Cys822Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.2e-06 in 237278 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2464T>C has been reported in the literature in individuals affected with Breast and Ovarian Cancer. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three 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 uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000077280 SCV000109077 uncertain significance Breast-ovarian cancer, familial 2 2011-01-24 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077280 SCV000146053 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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