Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000233086 | SCV000289706 | uncertain significance | Familial cancer of breast | 2020-04-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 240754). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with asparagine at codon 26 of the CHEK2 protein (p.Thr26Asn). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and asparagine. 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: "Benign"; Align-GVGD: "Class C0"). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192413 | SCV001360508 | uncertain significance | not specified | 2019-06-20 | criteria provided, single submitter | clinical testing | Variant summary: CHEK2 c.77C>A (p.Thr26Asn) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 248868 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.77C>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002411054 | SCV002673297 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-20 | criteria provided, single submitter | clinical testing | The p.T26N variant (also known as c.77C>A), located in coding exon 1 of the CHEK2 gene, results from a C to A substitution at nucleotide position 77. The threonine at codon 26 is replaced by asparagine, 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. |