ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4823A>C (p.Glu1608Ala)

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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 RCV002338033 SCV002637911 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-21 criteria provided, single submitter clinical testing The p.E1608A variant (also known as c.4823A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 4823. The glutamic acid at codon 1608 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. 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 RCV002338033 SCV003852124 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).
All of Us Research Program, National Institutes of Health RCV004005676 SCV004845735 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-08-28 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with alanine at codon 1608 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has been identified in 2/250098 chromosomes 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.

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