ClinVar Miner

Submissions for variant NM_003560.4(PLA2G6):c.2233C>T (p.Arg745Trp)

gnomAD frequency: 0.00001  dbSNP: rs587784350
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147317 SCV000194690 pathogenic Iron accumulation in brain 2013-02-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003507259 SCV004300017 pathogenic Infantile neuroaxonal dystrophy 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 745 of the PLA2G6 protein (p.Arg745Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of infantile neuroaxonal dystrophy (PMID: 16783378, 24800972, 29859652). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 159762). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PLA2G6 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Lab, CHRU Brest RCV003883135 SCV004697615 likely pathogenic Infantile neuroaxonal dystrophy; Neurodegeneration with brain iron accumulation 2B; Autosomal recessive Parkinson disease 14 criteria provided, single submitter clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000985141 SCV001133130 likely pathogenic Neurodegeneration with brain iron accumulation 2B 2019-09-26 no assertion criteria provided clinical testing

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