Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000178190 | SCV000230206 | uncertain significance | not provided | 2015-04-21 | criteria provided, single submitter | clinical testing | |
Lupski Lab, |
RCV000203270 | SCV000256753 | pathogenic | Pontocerebellar hypoplasia type 1A | 2013-10-14 | criteria provided, single submitter | research | Segregates with the phenotype in affected family |
Ambry Genetics | RCV000624198 | SCV000742629 | uncertain significance | Inborn genetic diseases | 2023-07-13 | criteria provided, single submitter | clinical testing | The c.266G>A (p.R89Q) alteration is located in exon 4 (coding exon 3) of the VRK1 gene. This alteration results from a G to A substitution at nucleotide position 266, causing the arginine (R) at amino acid position 89 to be replaced by a glutamine (Q). Based on data from gnomAD, the A allele has an overall frequency of 0.003% (8/251114) total alleles studied. The highest observed frequency was 0.023% (8/34566) of Latino alleles. The VRK1 c.266G>A (p.R89Q) alteration has been reported in the compound heterozygous state along with another missense variant in two sisters presenting with delayed motor development, microcephaly and normal cognition. The older sister had hypotonia, progressive scoliosis, progressive muscle wasting and weakness leading to the use of a wheelchair beginning at age 4, respiratory dysfunction and limited use of her arms and hands. Her brain MRI showed a simplified gyral pattern and EMG studies showed evidence of severe axonal motor and sensory peripheral neuropathy. The younger sister had microcephaly identified in utero as well as similar brain MRI and EMG findings, but she had normal muscle bulk (Gonzaga-Jauregui, 2013). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV000203270 | SCV000826524 | pathogenic | Pontocerebellar hypoplasia type 1A | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 89 of the VRK1 protein (p.Arg89Gln). This variant is present in population databases (rs773138218, gnomAD 0.02%). This missense change has been observed in individuals with VRK1-related conditions (PMID: 24126608; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 197213). 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. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000203270 | SCV001522969 | likely pathogenic | Pontocerebellar hypoplasia type 1A | 2020-01-17 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Revvity Omics, |
RCV000178190 | SCV002024796 | likely pathogenic | not provided | 2019-07-12 | criteria provided, single submitter | clinical testing | |
OMIM | RCV003387512 | SCV004098883 | pathogenic | Neuronopathy, distal hereditary motor, autosomal recessive 10 | 2013-12-01 | no assertion criteria provided | literature only |