ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6295A>G (p.Arg2099Gly) (rs398122551)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222158 SCV000273912 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Invitae RCV000695728 SCV000824243 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 2099 of the BRCA2 protein (p.Arg2099Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs398122551, ExAC 0.01%). This variant has been reported in a cohort of individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 21120943). ClinVar contains an entry for this variant (Variation ID: 91442). 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 glycine 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000076959 SCV000296497 uncertain significance Breast-ovarian cancer, familial 2 2016-06-10 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000076959 SCV000108756 uncertain significance Breast-ovarian cancer, familial 2 2011-06-28 no assertion criteria provided clinical testing

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