Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001019366 | SCV001180714 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-10-15 | criteria provided, single submitter | clinical testing | The c.945+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 6 in the PTCH1 gene. This nucleotide position is highly conserved in available vertebrate species. A similar alteration at this location, c.945+5G>T (designated as 933+5G>T) has been reported in an individual with features consistent with Nevoid Basal Cell Carcinoma Syndrome, also known as Gorlin syndrome (Fujii K et al. Hum. Mutat., 2003 Apr;21:451-2). Using the BDGP and ESEfinder splice site prediction tools, this alteration 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. |