ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7267G>A (p.Val2423Ile)

gnomAD frequency: 0.00001  dbSNP: rs1393996926
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000637535 SCV000758998 uncertain significance Hereditary breast ovarian cancer syndrome 2017-08-14 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This sequence change replaces valine with isoleucine at codon 2423 of the BRCA2 protein (p.Val2423Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine.
Ambry Genetics RCV002386028 SCV002672063 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-19 criteria provided, single submitter clinical testing The p.V2423I variant (also known as c.7267G>A), located in coding exon 13 of the BRCA2 gene, results from a G to A substitution at nucleotide position 7267. The valine at codon 2423 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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