ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1401G>C (p.Lys467Asn) (rs276174808)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA2) RCV000112917 SCV000145866 uncertain significance Breast-ovarian cancer, familial 2 2010-12-17 no assertion criteria provided clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587440 SCV000694536 uncertain significance not provided 2016-11-21 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1401G>C (p.Lys467Asn) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. One clinical diagnostic laboratory/reputable database classified this variant as uncertain significance. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000545323 SCV000635159 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-07-17 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 467 of the BRCA2 protein (p.Lys467Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. 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: 125944). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.

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