ClinVar Miner

Submissions for variant NM_003560.4(PLA2G6):c.1699G>A (p.Glu567Lys)

gnomAD frequency: 0.00001  dbSNP: rs587784337
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 RCV000147298 SCV000194671 pathogenic Iron accumulation in brain 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV002253241 SCV002525380 uncertain significance not provided 2022-05-24 criteria provided, single submitter clinical testing Observed with a second PLA2G6 variant, phase unknown, in an individual with infantile neuroaxonal dystrophy with brain iron in the published literature (Morgan et al., 2006); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26828213, 16783378, 30363890, 31540697)
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV002514836 SCV003760981 uncertain significance PLA2G6-associated neurodegeneration 2023-01-24 criteria provided, single submitter curation The p.Glu567Lys variant in PLA2G6 has been reported in 1 individual, in the compound heterozygous state, with PLA2G6-associated neurodegeneration (PMID: 16783378), and has been identified in 0.009% (3/34590) of Latino/Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs587784337). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 159743) and has been interpreted as pathogenic by Genetic Services Laboratory (University of Chicago). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein In summary, the clinical significance of the p.Glu567Lys variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting (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.