Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012985 | SCV001173515 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-31 | criteria provided, single submitter | clinical testing | The c.1744-3T>G pathogenic intronic variant results from a T to G substitution 3 nucleotides upstream from coding exon 14 in the APC gene. This alteration has been observed in multiple individuals who have a personal or family history that is consistent with APC-associated disease (Ambry internal data; Plawski A et al. J. Appl. Genet., 2008;49:407-14). This nucleotide position is well conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice acceptor site, and is predicted to weaken (but not abolish) the efficiency of the native splice acceptor site by ESEfinder. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). A close match alteration, APC c.1744-4C>G, also results in a similar splice defect and has been detected in individuals who have a personal or family history that is consistent with APC-associated disease (Ambry internal data). Based on the majority of available evidence to date, this alteration is interpreted as a disease-causing mutation. |