Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000635820 | SCV000757244 | likely pathogenic | Familial cancer of breast | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 11 of the CHEK2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. 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: 530142). Studies have shown that disruption of this splice site results in skipping of exon 11(aka. exon 10) and introduces a premature termination codon (PMID: 26506619). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |