ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3995A>G (p.His1332Arg) (rs398122774)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165461 SCV000216191 uncertain significance Hereditary cancer-predisposing syndrome 2014-08-22 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 RCV000545850 SCV000635325 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 1332 of the BRCA2 protein (p.His1332Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 91811). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000077719 SCV000109522 uncertain significance Breast-ovarian cancer, familial 2 2007-09-25 no assertion criteria provided clinical testing

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