ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3826G>A (p.Glu1276Lys) (rs878853575)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506737 SCV000600564 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
Invitae RCV000546808 SCV000635314 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1276 of the BRCA2 protein (p.Glu1276Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer in the Leiden Open-source Variation Database (PMID: 21520333). 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 lysine 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, 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 RCV000563847 SCV000665132 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)

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