ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4736C>T (p.Ala1579Val) (rs1555283920)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000545121 SCV000635401 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-21 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1579 of the BRCA2 protein (p.Ala1579Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a BRCA2-related disease. 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 valine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on BRCA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000562970 SCV000666174 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Color RCV000562970 SCV000688888 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758899 SCV000887825 uncertain significance not provided 2018-03-27 criteria provided, single submitter clinical testing

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