Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001121579 | SCV000934389 | uncertain significance | Pontocerebellar hypoplasia type 1A | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the VRK1 gene. It does not directly change the encoded amino acid sequence of the VRK1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs746546400, gnomAD 0.01%). 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: 641662). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
Illumina Laboratory Services, |
RCV001121579 | SCV001280209 | uncertain significance | Pontocerebellar hypoplasia type 1A | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Ambry Genetics | RCV002397585 | SCV002705774 | uncertain significance | Inborn genetic diseases | 2019-10-30 | criteria provided, single submitter | clinical testing | The c.161-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 2 in the VRK1 gene. This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by ESEfinder to abolish the native splice acceptor site, but is not predicted to have a deleterious effect on this splice acceptor site by BDGP; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV000794951 | SCV001466018 | uncertain significance | Congenital pontocerebellar hypoplasia type 1 | 2020-10-30 | no assertion criteria provided | clinical testing |