Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001280640 | SCV001467876 | uncertain significance | not specified | 2020-12-10 | criteria provided, single submitter | clinical testing | Variant summary: CNTN2 c.940C>T (p.Arg314X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay. The variant was absent in 246806 control chromosomes (gnomAD). To our knowledge, no occurrence of c.940C>T in individuals affected with Epilepsy, Familial Adult Myoclonic, 5 (FAME5) and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Though another truncating variant, c.504delG (p.Trp168fsX163), has been reported in homozygous state in affected individuals (PMID 23518707), suggesting that CNTN2 could be a candidate causative gene for an autosomal recessive disease phenotype (FAME5), however the current evidence is not sufficient to clearly establish whether loss-of-function variants in CNTN2 cause disease. Based on the evidence outlined above, the variant was classified as uncertain significance, until additional information becomes available. |
| Invitae | RCV001871613 | SCV002231762 | pathogenic | Epilepsy, familial adult myoclonic, 5 | 2021-04-30 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg314*) in the CNTN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNTN2 are known to be pathogenic (PMID: 11178983, 23518707). This variant has not been reported in the literature in individuals with CNTN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 992243). For these reasons, this variant has been classified as Pathogenic. |