Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000567692 | SCV000661693 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-07-14 | criteria provided, single submitter | clinical testing | The c.684-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 5 of the CHEK2 gene. 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; however, direct evidence is insufficient at this time (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. |
| Invitae | RCV000806075 | SCV000946056 | likely pathogenic | Familial cancer of breast | 2023-10-11 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 5 of the CHEK2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). This variant is present in population databases (no rsID available, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with breast cancer and/or pancreatic cancer (PMID: 30287823, 32980694). This variant is also known as c.813-1G>A. ClinVar contains an entry for this variant (Variation ID: 479534). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Myriad Genetics, |
RCV000806075 | SCV004042896 | likely pathogenic | Familial cancer of breast | 2023-06-26 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| Baylor Genetics | RCV000806075 | SCV004217678 | likely pathogenic | Familial cancer of breast | 2023-05-18 | criteria provided, single submitter | clinical testing | |
| CZECANCA consortium | RCV001270938 | SCV001451742 | pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | case-control | |
| University Health Network, |
RCV000806075 | SCV001738498 | likely pathogenic | Familial cancer of breast | 2021-03-19 | no assertion criteria provided | clinical testing | |
| Laboratory for Genotyping Development, |
RCV003159957 | SCV002758246 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |