Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001266696 | SCV001444873 | pathogenic | Inborn genetic diseases | 2020-12-01 | criteria provided, single submitter | clinical testing | The c.495-2A>G intronic alteration consists of a A to G substitution two nucleotides before exon 5 (coding exon 4) of the RSRC1 gene. 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. Based on data from the Genome Aggregation Database (gnomAD), the RSRC1 c.495-2A>G alteration was not observed, with coverage at this position. The c.495-2A nucleotide is conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Based on the available evidence, this alteration is classified as pathogenic. |