ClinVar Miner

Submissions for variant NM_004562.3(PRKN):c.850G>C (p.Gly284Arg)

gnomAD frequency: 0.00001  dbSNP: rs751037529
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000460040 SCV000549204 pathogenic not provided 2023-07-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 284 of the PRKN protein (p.Gly284Arg). This variant is present in population databases (rs751037529, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive early-onset Parkinson disease (PMID: 12973932, 15642853, 18554280, 20399249, 24831986, 25045378, 27177722). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 409266). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRKN protein function. Experimental studies have shown that this missense change affects PRKN function (PMID: 26161729). For these reasons, this variant has been classified as Pathogenic.
Developmental and Behavioral Pediatrics, First Affiliated Hospital of Jilin University RCV003326436 SCV003838969 pathogenic Autosomal recessive juvenile Parkinson disease 2 no assertion criteria provided clinical testing
Gene Friend Way, National Innovation Center RCV003313956 SCV004013894 pathogenic Autism spectrum disorder 2023-07-28 no assertion criteria provided clinical testing This missense change has been observed in individuals with autosomal recessive early-onset Parkinson disease (PMID: 12973932, 15642853, 18554280, 20399249, 24831986, 25045378, 27177722). Experimental studies have shown that this missense change affected PRKN function (PMID: 26161729). In addition, the loss of the Prkn gene in mice resulted in autistic-like behaviors, accompanied with altered neuronal activity, abnormalities in synapse formation and synaptic molecular composition (PMID: 35789851). Disfunctional PARK2 may be associated with Autism Spectrum Disorder (ASD) (PMID: 36478299). In our study, a child diagnosed with ASD carries this PRKN rs751037529 mutation.

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