ClinVar Miner

Submissions for variant NM_003560.4(PLA2G6):c.416G>A (p.Arg139His)

gnomAD frequency: 0.00038  dbSNP: rs141825182
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000585504 SCV000576575 uncertain significance not provided 2017-04-27 criteria provided, single submitter clinical testing The R139H variant in the PLA2G6 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R139H variant is observed in 60/41988 (0.14%) alleles from individuals of non-Finnish European background in the ExAC dataset, and no individuals were reported to be homozygous (Lek et al., 2016). The R139H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R139H as a variant of uncertain significance.
CeGaT Center for Human Genetics Tuebingen RCV000585504 SCV000693088 uncertain significance not provided 2023-07-01 criteria provided, single submitter clinical testing PLA2G6: PM2, BP4
Fulgent Genetics, Fulgent Genetics RCV000765651 SCV000896980 uncertain significance Infantile neuroaxonal dystrophy; Neurodegeneration with brain iron accumulation 2B; Autosomal recessive Parkinson disease 14 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001083799 SCV001006408 likely benign Infantile neuroaxonal dystrophy 2024-02-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001150840 SCV001311933 uncertain significance PLA2G6-associated neurodegeneration 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Mayo Clinic Laboratories, Mayo Clinic RCV000585504 SCV004225619 uncertain significance not provided 2023-06-09 criteria provided, single submitter clinical testing BP4

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