Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000990441 | SCV001141430 | likely pathogenic | Infantile neuroaxonal dystrophy | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000990441 | SCV001451504 | likely pathogenic | Infantile neuroaxonal dystrophy | 2019-02-14 | criteria provided, single submitter | clinical testing | The PLA2G6 c.1778C>T (p.Pro593Leu) variant is a missense variant that has been reported in one study, in which it is found in a total of one compound heterozygous individual (Al-Maawali et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.000062 in the African population of the Genome Aggregation Database, but this is based on one allele in a region of good sequence coverage, so the variant is presumed to be rare. The variant is in the PNPLA domain of the protein and is predicted to be damaging by SIFT, Polyphen, and REVEL. Based on the location of the variant, its rarity, identification in an affected individual, and in silico predictions, the p.Pro593Leu variant is classified as likely pathogenic for infantile neuroaxonal dystrophy 1. |
| Broad Center for Mendelian Genomics, |
RCV002549744 | SCV003760977 | uncertain significance | PLA2G6-associated neurodegeneration | 2023-01-24 | criteria provided, single submitter | curation | The p.Pro593Leu variant in PLA2G6 has been reported in 1 individual, in the compound heterozygous state, with PLA2G6-associated neurodegeneration (PMID: 27516098), and has been identified in 0.006% (1/16208) of African/African American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1451486649). 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#: 803690) and has been interpreted as likely pathogenic by Mendelics and Illumina Laboratory Services (Illumina). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Pro593Leu variant is uncertain. ACMG/AMP Criteria applied: PP3, PM2_supporting (Richards 2015). |