ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2345T>A (p.Leu782Gln)

dbSNP: rs876661019
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000215981 SCV000279212 uncertain significance not provided 2015-11-14 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2345T>A at the cDNA level, p.Leu782Gln (L782Q) at the protein level, and results in the change of a Leucine to a Glutamine (CTA>CAA). Using alternate nomenclature, this variant would be defined as BRCA2 2573T>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Leu782Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Leucine and Glutamine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Leu782Gln occurs at a position that is not conserved and is located in the region of interaction with NPM1 (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Leu782Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157467 SCV003848243 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 RCV003157467 SCV005025052 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-14 criteria provided, single submitter clinical testing The p.L782Q variant (also known as c.2345T>A), located in coding exon 10 of the BRCA2 gene, results from a T to A substitution at nucleotide position 2345. The leucine at codon 782 is replaced by glutamine, 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. Based on the available evidence, the clinical significance of this alteration remains unclear.

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