Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002001968 | SCV002215800 | pathogenic | Holoprosencephaly 5 | 2022-07-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ZIC2 protein in which other variant(s) (p.Lys410_His411del) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1435952). This variant has not been reported in the literature in individuals affected with ZIC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val386Serfs*27) in the ZIC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 147 amino acid(s) of the ZIC2 protein. |