ClinVar Miner

Submissions for variant NM_003560.4(PLA2G6):c.2222G>A (p.Arg741Gln) (rs121908686)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000811054 SCV000951300 pathogenic Infantile neuroaxonal dystrophy 2018-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 741 of the PLA2G6 protein (p.Arg741Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs121908686, ExAC 0.05%). This variant has been observed to segregate with dystonia-parkinsonism in several families (PMID: 18570303, 27268037, 20669327) and reported in other unrelated affected individuals (PMID: 26668131, 26196026). ClinVar contains an entry for this variant (Variation ID: 6203). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000006581 SCV001132758 likely pathogenic Parkinson disease 14 2019-12-02 criteria provided, single submitter clinical testing A homozygous missense variation in exon 16 of the PLA2G6 gene that results in the amino acid substitution of Glutamine for Arginine at codon 741 was detected. The observed variation has not been reported in 1000 genomes and has a minor allele frequency of 0.02% in ExAc database. The in silico predictions of the variant are probably damaging by Polyphen-2 (HumDiv) and damaging by Mutation Taster2. The reference codon is conserved across mammals. The observed variant has previously been observed in patients with adult onset dystonia Parkinsonism (Pasian-Ruiz et al. 2009). In summary, the variant meets our criteria to be classified as likely pathogenic.
Centogene AG - the Rare Disease Company RCV001251187 SCV001426573 pathogenic Neurodegeneration with brain iron accumulation 2b criteria provided, single submitter clinical testing
Genomics England Pilot Project,Genomics England RCV000006581 SCV001760488 likely pathogenic Parkinson disease 14 criteria provided, single submitter clinical testing
GeneDx RCV001588801 SCV001814453 likely pathogenic not provided 2020-05-27 criteria provided, single submitter clinical testing Functional analyses have not demonstrated a consistent damaging effect of this variant on protein activity (Engel et al., 2010; Chiu et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32707456, 24182522, 31196701, 26196026, 20669327, 26668131, 18570303, 27268037, 25601130, 29108286, 20886109)
OMIM RCV000006581 SCV000026764 pathogenic Parkinson disease 14 2009-02-01 no assertion criteria provided literature only

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