Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001027112 | SCV001189618 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-03 | criteria provided, single submitter | clinical testing | The c.80-5_82DELCTCAGATA variant spans the canonical acceptor site of coding exon 2 in the PTEN gene. This variant results from a deletion of 8 nucleotides at positions c.80-5 to c.82. The canonical acceptor site is highly conserved in available vertebrate species. The BDGP and ESEfinder splice site prediction tools are not able to produce a reliable prediction for the nearby native splice acceptor site. Using the Human Splicing Finder (HSF) splice site prediction tool, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable (Desmet FO et al. Nucleic Acids Res. 2009 May;37:e67). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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. |