ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6811A>G (p.Lys2271Glu)

dbSNP: rs876661276
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000220206 SCV000279957 uncertain significance not provided 2016-03-03 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6811A>G at the cDNA level, p.Lys2271Glu (K2271E) at the protein level, and results in the change of a Lysine to a Glutamic Acid (AAA>GAA). Using alternate nomenclature, this variant would be defined as BRCA2 7039A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Lys2271Glu 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 Lysine and Glutamic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Lys2271Glu occurs at a position that is conserved across species and is not located in a known functional domain (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Lys2271Glu 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 RCV003157470 SCV003847468 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 RCV003157470 SCV005097495 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-08 criteria provided, single submitter clinical testing The p.K2271E variant (also known as c.6811A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6811. The lysine at codon 2271 is replaced by glutamic acid, an amino acid with 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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