Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000575171 | SCV000666368 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-30 | criteria provided, single submitter | clinical testing | The p.S16R variant (also known as c.46A>C), located in coding exon 1 of the CHEK2 gene, results from an A to C substitution at nucleotide position 46. The serine at codon 16 is replaced by arginine, an amino acid with dissimilar 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. |
Color Diagnostics, |
RCV000575171 | SCV000912423 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001308832 | SCV001498304 | uncertain significance | Familial cancer of breast | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 16 of the CHEK2 protein (p.Ser16Arg). This variant is present in population databases (no rsID available, 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: 481719). 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. |
Gene |
RCV001560729 | SCV001783198 | uncertain significance | not provided | 2019-05-28 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |