Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213314 | SCV000273595 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-08-06 | criteria provided, single submitter | clinical testing | The c.221-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 3 of the APC 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 and will result in the creation or strengthening of a novel splice acceptor site. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Another alteration impacting the same acceptor site (c.221-1G>A) has been detected in individuals with FAP/AFAP (Woods MO et al. Gut, 2010 Oct;59:1369-77; 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. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV003462425 | SCV000552771 | pathogenic | Familial adenomatous polyposis 1 | 2023-01-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 230154). This variant is also known as IVS3-1G>C. Disruption of this splice site has been observed in individual(s) with familial adenomatous polyposis (PMID: 19029688). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 3 of the APC gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. |
| Myriad Genetics, |
RCV003462425 | SCV004045731 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-04-25 | 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 | RCV003462425 | SCV004208095 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-11-22 | criteria provided, single submitter | clinical testing |