Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Knight Diagnostic Laboratories, |
RCV000454340 | SCV000538018 | likely pathogenic | Lethal multiple pterygium syndrome | 2016-03-24 | criteria provided, single submitter | clinical testing | The c.1374_1375delGA (p. Lys459Argfs*113) frameshift variant in the CHRND gene has not been previously reported. This variant is predicted to result in the loss of a stop codon or loss of the splice acceptor site in the last exon of this gene, which contains a ligand-gated ion channel domain. Multiple in silico algorithms predict this variant to have a deleterious effect (GERP=5.13, Human Splicing Finder v3.0 predicts creation of a new splice acceptor). This variant is absent from the population databases (Exome Sequencing Project; 1000 Genomes; and ExAC). One family with multiple affected individuals that are compound heterozygous for a nonsense variant (p.Arg464*), which is downstream of this variant and a missense variant (p.Phe74Leu) has been reported (Michalk et al., 2008). Therefore, this collective evidence supports the classification of c.1374_1375delGA (p. Lys459Argfs*113) as a Likely pathogenic variant for Lethal Multiple Pterygium Syndrome. We have confirmed this finding in our laboratory using Sanger sequencing. |