Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002389683 | SCV002700899 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-08 | criteria provided, single submitter | clinical testing | The p.D497G variant (also known as c.1490A>G), located in coding exon 13 of the CHEK2 gene, results from an A to G substitution at nucleotide position 1490. The aspartic acid at codon 497 is replaced by glycine, an amino acid with similar properties. This amino acid position is poorly 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. |
| Baylor Genetics | RCV003465725 | SCV004217552 | uncertain significance | Familial cancer of breast | 2023-09-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003465725 | SCV004384323 | uncertain significance | Familial cancer of breast | 2023-09-03 | criteria provided, single submitter | clinical testing | 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 aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 497 of the CHEK2 protein (p.Asp497Gly). This variant is present in population databases (rs549945536, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1773766). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. |