Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000664468 | SCV000788430 | likely pathogenic | Peroxisome biogenesis disorder 5A (Zellweger); Peroxisome biogenesis disorder 5B | 2017-08-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780588 | SCV000917985 | pathogenic | Peroxisome biogenesis disorder | 2018-06-04 | criteria provided, single submitter | clinical testing | Variant summary: PEX2 c.373C>T (p.Arg125X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8.2e-06 in 121346 control chromosomes. c.373C>T has been reported in the literature in individuals with biochemically confirmed Zellweger Syndrome . These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV001053880 | SCV001218163 | pathogenic | Peroxisome biogenesis disorder 5A (Zellweger) | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg125*) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 181 amino acid(s) of the PEX2 protein. This variant is present in population databases (rs61752124, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome (PMID: 9452066, 21465523). ClinVar contains an entry for this variant (Variation ID: 549898). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects PEX2 function (PMID: 10528859). This variant disrupts the C-terminus of the PEX2 protein. Other variant(s) that disrupt this region (p.Arg184Valfs*8, p.Trp223* p.Phe278Leufs*3, p.Ser289Lysfs*36) have been observed in individuals with PEX2-related conditions (PMID: 10652207, 14630978, 17041890). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV000664468 | SCV002811525 | pathogenic | Peroxisome biogenesis disorder 5A (Zellweger); Peroxisome biogenesis disorder 5B | 2021-09-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003231574 | SCV003930143 | pathogenic | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | In vitro studies demonstrate the p.R125* variant has a deleterious effect on protein function with severely reduced PEX2 activity (Shimozawa et al., 1999); Nonsense variant predicted to result in protein truncation, as the last 181 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17045664, 11330042, 21465523, 9375798, Vo2021[abstract], Ranganath2022[abstract], 21031596, 9452066, 15542397, 10528859) |
Baylor Genetics | RCV001053880 | SCV004201463 | pathogenic | Peroxisome biogenesis disorder 5A (Zellweger) | 2023-10-26 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001275871 | SCV001461518 | pathogenic | Zellweger spectrum disorders | 2020-09-16 | no assertion criteria provided | clinical testing | |
Center of Excellence for Medical Genomics, |
RCV002281578 | SCV002570023 | pathogenic | Peroxisome biogenesis disorder 5B | 2002-09-08 | no assertion criteria provided | research |