Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002519586 | SCV000647210 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-05-22 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 15 of the APC 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 APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with familial adenomatous polyposis (PMID: 20685668). ClinVar contains an entry for this variant (Variation ID: 217939). 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. |
| Ambry Genetics | RCV002415860 | SCV002720086 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-11-23 | criteria provided, single submitter | clinical testing | The c.1959-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 15 in the APC gene. This mutation was detected once in a large cohort of French FAP patients (Lagarde, A et al. J Med Genet. 2010 Oct;47(10):721-2). Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct experimental evidence is unavailable. In addition to the clinical data presented in the literature, 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 a disease-causing mutation. |
| Myriad Genetics, |
RCV002519586 | SCV004044754 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-05-03 | 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. |
| Mayo Clinic Laboratories, |
RCV000202143 | SCV000256936 | pathogenic | not provided | no assertion criteria provided | research |