Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000822473 | SCV000963276 | pathogenic | Familial cancer of breast | 2020-10-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). This variant has not been reported in the literature in individuals with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 664385). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro90Leufs*20) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV001016347 | SCV001177294 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-23 | criteria provided, single submitter | clinical testing | The c.269delC pathogenic mutation, located in coding exon 1 of the CHEK2 gene, results from a deletion of one nucleotide at nucleotide position 269, causing a translational frameshift with a predicted alternate stop codon (p.P90Lfs*20). 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. |