Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000203880 | SCV000261331 | likely pathogenic | Familial cancer of breast | 2015-10-19 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 2. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV003165500 | SCV003858989 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-04-19 | criteria provided, single submitter | clinical testing | The c.320-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 2 of the CHEK2 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and may result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |