Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001004414 | SCV001163450 | pathogenic | Infantile neuroaxonal dystrophy | criteria provided, single submitter | clinical testing | ||
Broad Center for Mendelian Genomics, |
RCV002549242 | SCV003761002 | likely pathogenic | PLA2G6-associated neurodegeneration | 2025-05-06 | criteria provided, single submitter | curation | The c.1187-1G>A variant in PLA2G6 has not been previously reported in the literature in individuals with PLA2G6-associated neurodegeneration, but has been identified in 0.00008% (1/1179968) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1477656610). 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#: 813443) and has been interpreted as pathogenic by Baylor Genetics. This variant is located in the 5' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. Loss of function of the PLA2G6 gene is an established disease mechanism in autosomal recessive PLA2G6-associated neurodegeneration. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive PLA2G6-associated neurodegeneration. ACMG/AMP Criteria applied: PVS1, PM2_supporting (Richards 2015). |