Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002378690 | SCV002684206 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-05-03 | criteria provided, single submitter | clinical testing | The c.911-8C>A intronic variant results from a C to A substitution 8 nucleotides upstream from coding exon 8 in the SUFU gene. This nucleotide position is poorly conserved in available vertebrate species, however adenine is not an observed substitution. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site. RNA studies have demonstrated this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). SUFU c.1022+1G>A is an alteration at the splice donor site of exon 8 and results in the same aberrant out-of-frame transcript lacking exon 8. This donor site alteration was identified in two individuals from the same family with features of Gorlin syndrome (Pastorino L et al. Am. J. Med. Genet. A, 2009 Jul;149A:1539-43). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |