Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000582748 | SCV000689738 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-09-02 | criteria provided, single submitter | clinical testing | This variant deletes 5 nucleotides in exon 8 of the CHEK2 gene, creating a frameshift and premature translation stop signal. This variant is also known as c.1022_1026del in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with breast and/or ovarian cancer (PMID: 30333958). 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. |
| Invitae | RCV000805624 | SCV000945587 | pathogenic | Familial cancer of breast | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr298Cysfs*12) 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: 491651). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000582748 | SCV002687561 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-07-16 | criteria provided, single submitter | clinical testing | The c.893_897delATATT pathogenic mutation, located in coding exon 7 of the CHEK2 gene, results from a deletion of 5 nucleotides at nucleotide positions 893 to 897, causing a translational frameshift with a predicted alternate stop codon (p.Y298Cfs*12). 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. |
| Myriad Genetics, |
RCV000805624 | SCV004044077 | pathogenic | Familial cancer of breast | 2023-06-27 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Center for Genomic Medicine, |
RCV003493676 | SCV004243021 | pathogenic | not provided | 2024-02-06 | criteria provided, single submitter | clinical testing |