ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4957A>G (p.Thr1653Ala) (rs587782186)

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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 RCV000130816 SCV000185712 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000130816 SCV000906095 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496784 SCV000591933 uncertain significance not specified 2014-09-10 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000496784 SCV000588095 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
Invitae RCV000637549 SCV000759013 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1653 of the BRCA2 protein (p.Thr1653Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 142026). 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 alanine 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000210984 SCV000267774 uncertain significance Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing

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