ClinVar Miner

Submissions for variant NM_003384.2(VRK1):c.266G>A (p.Arg89Gln) (rs773138218)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624198 SCV000742629 uncertain significance Inborn genetic diseases 2017-06-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000178190 SCV000230206 uncertain significance not provided 2015-04-21 criteria provided, single submitter clinical testing
Invitae RCV000697891 SCV000826524 likely pathogenic Pontocerebellar hypoplasia type 1 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 89 of the VRK1 protein (p.Arg89Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs773138218, ExAC 0.009%). This variant has been reported to segregate with motor and sensory axonal neuropathy plus microcephaly in a family (PMID: 24126608) and has been reported in individuals affected with VRK1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 197213). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Lupski Lab, Baylor-Hopkins CMG,Baylor College of Medicine RCV000203270 SCV000256753 pathogenic Pontocerebellar hypoplasia type 1A 2013-10-14 criteria provided, single submitter research Segregates with the phenotype in affected family

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