ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6941C>A (p.Thr2314Lys) (rs1177474377)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000587992 SCV000695003 uncertain significance not provided 2016-03-21 criteria provided, single submitter clinical testing Variant summary: c.6941C>A affects a non-conserved nucleotide, resulting in amino acid change from Thr to Lys. 5/5 in-silico tools predict this variant to be damaging. This variant was found in 1/115324 control chromosomes at a frequency of 0.0000087, which does not exceed the maximal expected frequency of a pathogenic allele (0.0007503). The variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical laboratories nor was evaluated for functional impact by in vivo/vitro studies. Due to the absence of clinical information and lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000690922 SCV000818653 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-03-05 criteria provided, single submitter clinical testing This sequence change replaces threonine with lysine at codon 2314 of the BRCA2 protein (p.Thr2314Lys). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and lysine. This variant is present in population databases (rs80359629, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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