Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323360 | SCV004028599 | likely pathogenic | Peroxisome biogenesis disorder | 2023-07-27 | criteria provided, single submitter | clinical testing | Variant summary: PEX2 c.163G>A (p.Glu55Lys) results in a conservative amino acid change to a highly conserved residue (HGMD) located in the Pex, N-terminal (IPR006845) of 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 251214 control chromosomes (gnomAD). c.163G>A has been reported in the literature in an individual affected with Refsum disease who was compound heterozygous with a pathogenic variant (Imamura_1998, Shimozawa_1999). These data suggest the variant may be associated with disease. At least two publications report experimental evidence evaluating an impact on protein function, finding that cells expressing the variant protein showed partially reduced enzymatic activity and recapitulated the catalase-less persoxisomes seen in patient cells (Fujiwara_2000, Shimozawa_1999). The following publications have been ascertained in the context of this evaluation (PMID: 9585609, 10528859, 10960480). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000014704 | SCV000034959 | pathogenic | Peroxisome biogenesis disorder 5B | 1999-10-01 | no assertion criteria provided | literature only |