ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6269A>G (p.His2090Arg) (rs397507366)

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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 RCV000562031 SCV000665106 likely benign Hereditary cancer-predisposing syndrome 2019-04-26 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene;In silico models in agreement (benign)
Color RCV000562031 SCV000688972 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-14 criteria provided, single submitter clinical testing
Counsyl RCV000031611 SCV000784901 uncertain significance Breast-ovarian cancer, familial 2 2017-02-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001175040 SCV001338562 uncertain significance not specified 2020-04-03 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6269A>G (p.His2090Arg) 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 4.1e-06 in 244318 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.6269A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV001214226 SCV001385899 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-06-17 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 2090 of the BRCA2 protein (p.His2090Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs397507366, ExAC 0.002%). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 38030). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Sharing Clinical Reports Project (SCRP) RCV000031611 SCV000054218 uncertain significance Breast-ovarian cancer, familial 2 2012-02-24 no assertion criteria provided clinical testing

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