ClinVar Miner

Submissions for variant NM_003384.3(VRK1):c.356A>G (p.His119Arg)

gnomAD frequency: 0.00003  dbSNP: rs371295780
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000191143 SCV000245552 likely pathogenic Pontocerebellar hypoplasia type 1A 2014-01-27 criteria provided, single submitter clinical testing Likely pathogenicity based on finding it once in our laboratory in trans with another missense variant [R321C] in a 33-year-old male with clinical diagnoses of distal spinal muscular atrophy and motor neuropathy.
GeneDx RCV000523462 SCV000618460 pathogenic not provided 2023-08-03 criteria provided, single submitter clinical testing Published functional studies demonstrate reduced kinase activity (Martin-Doncel et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26633545, 35641352, 31090908, 26583493, 27281532, 37257665, 34169149, 31589614, RodriguezHrnandez2023[abstract], 31527692)
Fulgent Genetics, Fulgent Genetics RCV000191143 SCV000893357 likely pathogenic Pontocerebellar hypoplasia type 1A 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000191143 SCV001588881 pathogenic Pontocerebellar hypoplasia type 1A 2024-02-16 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 119 of the VRK1 protein (p.His119Arg). This variant is present in population databases (rs371295780, gnomAD 0.01%). This missense change has been observed in individual(s) with adult onset distal spinal muscular atrophy (PMID: 26583493, 27281532). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 209204). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects VRK1 function (PMID: 31527692). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005008123 SCV005630511 likely pathogenic Pontocerebellar hypoplasia type 1A; Neuronopathy, distal hereditary motor, autosomal recessive 10 2024-02-22 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.