Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019181 | SCV001180507 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-24 | criteria provided, single submitter | clinical testing | The c.933+2T>G intronic variant results from a T to G substitution two nucleotides after coding exon 8 in the APC gene. A similar alteration affecting the same nucleotide, c.933+2T>C, has been reported as segregating with a classic familial adenomatous polyposis (FAP) phenotype in one family (Aretz et al. Human Mutat. 2004 Nov;24(5):370-80) and was also identified in 1/863 French patients with FAP (Lagarde A et al. J. Med. Genet., 2010 Oct;47:721-2). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, c.933+2T>G is predicted to abolish the native splice donor 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. |
| Myriad Genetics, |
RCV003337345 | SCV004045070 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-04-28 | 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. |