ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4642G>A (p.Glu1548Lys)

dbSNP: rs1566230862
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759619 SCV000889055 uncertain significance not provided 2018-04-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000791852 SCV000931118 uncertain significance Hereditary breast ovarian cancer syndrome 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1548 of the BRCA2 protein (p.Glu1548Lys). The glutamic acid residue is highly 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 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158108 SCV003850677 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003158108 SCV005027235 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-19 criteria provided, single submitter clinical testing The p.E1548K variant (also known as c.4642G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 4642. The glutamic acid at codon 1548 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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