Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000779151 | SCV000915662 | uncertain significance | Pontocerebellar hypoplasia type 1A | 2017-11-29 | criteria provided, single submitter | clinical testing | The VRK1 c.1174_1177delAAGA (p.Lys392GlufsTer34) variant results in a frameshift, and is predicted to result in an elongation of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for pontocerebellar hypoplasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Labcorp Genetics |
RCV000779151 | SCV003499081 | uncertain significance | Pontocerebellar hypoplasia type 1A | 2022-02-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys392Glufs*34) in the VRK1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the VRK1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VRK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 632224). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |