Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000204142 | SCV000260530 | uncertain significance | Familial cancer of breast | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 385 of the CHEK2 protein (p.Cys385Tyr). This variant is present in population databases (rs145324174, gnomAD 0.007%). 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: 220179). 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 disruptive. 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 |
RCV000481497 | SCV000570242 | uncertain significance | not provided | 2021-11-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22419737, 19782031) |
Ambry Genetics | RCV000574409 | SCV000661706 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-03 | criteria provided, single submitter | clinical testing | The p.C385Y variant (also known as c.1154G>A), located in coding exon 10 of the CHEK2 gene, results from a G to A substitution at nucleotide position 1154. The cysteine at codon 385 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798682 | SCV002043390 | uncertain significance | Breast and/or ovarian cancer | 2021-01-04 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003407726 | SCV004112578 | uncertain significance | CHEK2-related condition | 2023-08-25 | criteria provided, single submitter | clinical testing | The CHEK2 c.1154G>A variant is predicted to result in the amino acid substitution p.Cys385Tyr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 3 of ~251,000 alleles in gnomAD (http://gnomad.broadinstitute.org/variant/22-29091803-C-T). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/220179/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Baylor Genetics | RCV000204142 | SCV004217581 | uncertain significance | Familial cancer of breast | 2023-08-30 | criteria provided, single submitter | clinical testing |