ClinVar Miner

Submissions for variant NM_003560.4(PLA2G6):c.2202+5G>A

dbSNP: rs587784348
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147315 SCV000194688 uncertain significance Iron accumulation in brain 2013-02-08 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001095728 SCV001251567 uncertain significance PLA2G6-associated neurodegeneration 2020-02-06 criteria provided, single submitter clinical testing The PLA2G6 c.2202+5G>A variant is a splice region variant. A literature search was performed for the gene and cDNA change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequencing coverage, so the variant is presumed to be rare. Based on the limited evidence, the c.2202+5G>A variant is classified as a variant of unknown significance for PLA2G6-associated neurodegeneration.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003225931 SCV003922101 uncertain significance Infantile neuroaxonal dystrophy 2023-05-02 criteria provided, single submitter curation The heterozygous c.2202+5G>A variant in PLA2G6 was identified by our study, in the compound heterozygous state with a pathogenic variant (ClinVar Variation ID: 159749), in one individual with generalized muscle weakness, hypotonia, delayed speech and language development, gait imbalance, and inability to walk. Trio exome analysis revealed that this variant was in trans with a pathogenic variant (ClinVar Variation ID: 159749). The c.2202+5G>A variant in PLA2G6 has not been previously reported in individuals with neurodegeneration with brain iron accumulation-2A. This variant was absent from large population studies. This variant has also been reported in ClinVar (Variation ID: 159760) and has been interpreted as a variant of uncertain significance by the University of Chicago Genetic Services Laboratory and Illumina. This variant is located in the 5' splice region. Computational tools do suggest an impact to splicing. However, this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PM3, PP3 (Richards 2015).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.