ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1277A>C (p.Lys426Thr) (rs1421854019)

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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 RCV000568483 SCV000661321 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000588909 SCV000694528 uncertain significance not provided 2017-08-21 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1277A>C (p.Lys426Thr) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict damaging outcome for this variant. This variant is absent in 120474 control chromosomes from ExAC. This variant has been found in one breast cancer patient who had positive family history (Solano_2016), however without strong evidence for or against pathogenicity. There are no functional studies published for this variant. Taken together, this variant is classified as Variant of Unknown Significance.
Invitae RCV000637322 SCV000758773 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-10-12 criteria provided, single submitter clinical testing This sequence change replaces lysine with threonine at codon 426 of the BRCA2 protein (p.Lys426Thr). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). 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: "Tolerated"; PolyPhen-2: "Possibly 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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