ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.37G>A (p.Glu13Lys) (rs80358622)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478846 SCV000565687 uncertain significance not provided 2016-03-29 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.37G>A at the cDNA level, p.Glu13Lys (E13K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). Using alternate nomenclature, this variant would be defined as BRCA2 265G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Glu13Lys 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 Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Glu13Lys occurs at a position where amino acids with properties similar to Glutamic Acid are tolerated across species and is not located in a known functional domain (Roy 2012). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Glu13Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000543750 SCV000635311 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-02-08 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 13 of the BRCA2 protein (p.Glu13Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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