ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3427G>A (p.Glu1143Lys)

gnomAD frequency: 0.00001  dbSNP: rs1316176181
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001177009 SCV001341114 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-16 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1143 of the BRCA2 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001177009 SCV002615552 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-30 criteria provided, single submitter clinical testing The p.E1143K variant (also known as c.3427G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 3427. The glutamic acid at codon 1143 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV001177009 SCV003851952 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).

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