Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000680067 | SCV000807507 | pathogenic | Infantile neuroaxonal dystrophy | criteria provided, single submitter | clinical testing | ||
| Labcorp Genetics |
RCV000680067 | SCV002144341 | pathogenic | Infantile neuroaxonal dystrophy | 2023-09-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 561083). This missense change has been observed in individuals with PLA2G6-related conditions (PMID: 16783378, 18799783, 25634434). It has also been observed to segregate with disease in related individuals. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 347 of the PLA2G6 protein (p.Gly347Arg). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235345 | SCV003933722 | pathogenic | Neurodegeneration with brain iron accumulation | 2023-05-17 | criteria provided, single submitter | clinical testing | Variant summary: PLA2G6 c.1039G>A (p.Gly347Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 158478 control chromosomes (gnomAD). c.1039G>A has been reported in the literature in multiple bi-allelic individuals affected with PLA2G6-related conditions and the variant segregated with the disease (examples: Gregory_2008 and Kim_2015). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 18799783, 25634434). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |