Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001179811 | SCV001344593 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant inserts 17 nucleotides in exon 11 of the CHEK2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CHEK2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Mendelics | RCV002249759 | SCV002518703 | pathogenic | Familial cancer of breast | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001179811 | SCV002744345 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-05 | criteria provided, single submitter | clinical testing | The c.1111_1127dup17 pathogenic mutation, located in coding exon 10 of the CHEK2 gene, results from a duplication of CACTCCAAGATTTTGGG at nucleotide position 1111, causing a translational frameshift with a predicted alternate stop codon (p.E377Tfs*11). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV002249759 | SCV003017582 | pathogenic | Familial cancer of breast | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu377Thrfs*11) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). 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: 920804). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV002249759 | SCV004044531 | pathogenic | Familial cancer of breast | 2023-06-28 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV002249759 | SCV004217696 | likely pathogenic | Familial cancer of breast | 2023-03-30 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV003992458 | SCV004810810 | pathogenic | not provided | 2024-03-01 | criteria provided, single submitter | clinical testing | CHEK2: PVS1, PM2 |