ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6660A>C (p.Glu2220Asp)

dbSNP: rs2137529521
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001982484 SCV002227282 uncertain significance Hereditary breast ovarian cancer syndrome 2021-07-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 2220 of the BRCA2 protein (p.Glu2220Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. 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 RCV003156889 SCV003847343 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 RCV003156889 SCV005102149 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-10 criteria provided, single submitter clinical testing The p.E2220D variant (also known as c.6660A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 6660. The glutamic acid at codon 2220 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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