Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000583579 | SCV000689733 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-05 | criteria provided, single submitter | clinical testing | This variant deletes 13 basepairs in the intron 7 splice acceptor site of the CHEK2 gene, including a canonical splice site nucleotide at the -2 position. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. However, other canonical splice site variants, impacting the -2 and -1 positions in this splice acceptor site, have been reported as disease-causing (ClinVar variation ID: 240758, 822474) and have been observed in two affected and two unaffected individuals in a breast cancer case-control study (PMID: 30287823). 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 Likely Pathogenic. |
| MGZ Medical Genetics Center | RCV002289861 | SCV002579926 | likely pathogenic | Familial cancer of breast | 2022-04-27 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000583579 | SCV002680633 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-04-12 | criteria provided, single submitter | clinical testing | The c.847-14_847-2del13 intronic variant results from a deletion of 13 nucleotides within intron 6 of the CHEK2 gene. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. 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. |