Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000203958 | SCV000261046 | uncertain significance | Familial cancer of breast | 2022-05-27 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 220477). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 126 of the CHEK2 protein (p.Asp126Gly). |
Gene |
RCV001753615 | SCV002005235 | uncertain significance | not provided | 2019-02-22 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002345739 | SCV002620433 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-26 | criteria provided, single submitter | clinical testing | The p.D126G variant (also known as c.377A>G), located in coding exon 2 of the CHEK2 gene, results from an A to G substitution at nucleotide position 377. The aspartic acid at codon 126 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |