Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570308 | SCV000669258 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-30 | criteria provided, single submitter | clinical testing | The p.D293A variant (also known as c.878A>C), located in coding exon 7 of the CHEK2 gene, results from an A to C substitution at nucleotide position 878. The aspartic acid at codon 293 is replaced by alanine, an amino acid with dissimilar properties. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284623 | SCV001470508 | uncertain significance | not provided | 2020-08-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001867889 | SCV002202146 | uncertain significance | Familial cancer of breast | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 293 of the CHEK2 protein (p.Asp293Ala). This variant is not present in population databases (gnomAD no frequency). 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: 483371). 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. 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. |