Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002866299 | SCV003227564 | uncertain significance | Familial cancer of breast | 2024-08-20 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the CHEK2 gene (p.Glu526Lysfs*40). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acid(s) of the CHEK2 protein and extend the protein by 21 additional amino acid residues. 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: 2021325). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Ambry Genetics | RCV004948808 | SCV005558600 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-26 | criteria provided, single submitter | clinical testing | The c.1576delG variant, located in coding exon 14 of the CHEK2 gene, results from a deletion of one nucleotide at nucleotide position 1576, causing a translational frameshift with a predicted alternate stop codon (p.E526Kfs*40). This alteration occurs at the 3' terminus of theCHEK2 gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein by 21 amino acids. This frameshift impacts the last 3.3% of the native protein. The exact functional effect of the altered amino acids is unknown. Based on the available evidence, the clinical significance of this variant remains unclear. |