Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Rady Children's Institute for Genomic Medicine, |
RCV003335959 | SCV004046368 | likely pathogenic | Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly | criteria provided, single submitter | clinical testing | This variant affects the canonical splice acceptor site of intron 7 and is therefore predicted to interfere with splicing and result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has not been previously reported or functionally characterized in the literature to our knowledge. A nearby splice site variant (c.902-2A>G) has been reported in individuals with atypical hemolytic uremic syndrome (PMID: 25525159, 17089378, 16762990). Loss-of-function variation in CD46 is an established mechanism of disease (PMID: 20301541). The c.902-1G>A variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.002% (7/282734) and thus is presumed to be rare. Based on the available evidence, the c.902-1G>A variant is classified as Likely Pathogenic. |