Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002570361 | SCV001421310 | pathogenic | Pontocerebellar hypoplasia type 1A | 2023-09-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the VRK1 protein in which other variant(s) (p.Arg387His) have been determined to be pathogenic (PMID: 31837156; 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 971948). This frameshift has been observed in individual(s) with clinical features of hereditary motor neuropathy (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the VRK1 gene (p.Thr378Ilefs*25). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acid(s) of the VRK1 protein and extend the protein by 5 additional amino acid residues. |