ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.10075G>A (p.Glu3359Lys)

dbSNP: rs777397727
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001016974 SCV001177987 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-14 criteria provided, single submitter clinical testing The p.E3359K variant (also known as c.10075G>A), located in coding exon 26 of the BRCA2 gene, results from a G to A substitution at nucleotide position 10075. The glutamic acid at codon 3359 is replaced by lysine, an amino acid with similar properties. This variant has been reported in a woman with breast cancer and ureter cancer (Sung PL et al. PLoS ONE, 2017 Sep;12:e0185615). This amino acid position is not well conserved in available vertebrate species. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV005093148 SCV005836293 uncertain significance Hereditary breast ovarian cancer syndrome 2024-08-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 3359 of the BRCA2 protein (p.Glu3359Lys). This variant is present in population databases (rs777397727, gnomAD 0.0009%). This missense change has been observed in individual(s) with breast cancer (PMID: 28961279). ClinVar contains an entry for this variant (Variation ID: 821998). 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 with a negative predictive value of 95%. 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.

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