ClinVar Miner

Submissions for variant NM_000318.3(PEX2):c.355C>T (p.Arg119Ter) (rs61752123)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000014703 SCV000487549 pathogenic Peroxisome biogenesis disorder 5a (zellweger) 2016-08-16 criteria provided, single submitter clinical testing
Counsyl RCV000032924 SCV000487550 pathogenic Peroxisome biogenesis disorder 5B 2016-08-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589554 SCV000696558 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2017-03-31 criteria provided, single submitter clinical testing Variant summary: The PEX2 c.355C>T (p.Arg119X) variant results in a premature termination codon, predicted to cause a truncated or absent PEX2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in the large control database ExAC and control cohorts in the literature at a frequency of 0.0002708 (34/125548 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX2 variant (0.001118). Several publications have cited the variant in patients with diagnoses that are confirmed with standard biochemical tests. Additionally, a functional study demonstrated a lack of peroxisome formation via immunofluorescence in cultured fibroblasts of a patient who was homozygous for the variant of interest (Imamura_AJHG_1998). Furthermore, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000014703 SCV000949919 pathogenic Peroxisome biogenesis disorder 5a (zellweger) 2018-12-04 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PEX2 gene (p.Arg119*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 187 amino acids of the PEX2 protein. This variant is present in population databases (rs61752123, ExAC 0.02%). This variant has been observed in individuals affected with Zellweger spectrum disorders (PMID: 1546315, 7681622, 9452066, 9585609, 15542397, 23430938). Fibroblasts derived from affected individuals showed peroxisome abnormalities in cell culture (PMID: 10528859, 21465523). ClinVar contains an entry for this variant (Variation ID: 13704). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014703 SCV000034958 pathogenic Peroxisome biogenesis disorder 5a (zellweger) 2014-04-01 no assertion criteria provided literature only
OMIM RCV000032924 SCV000056696 pathogenic Peroxisome biogenesis disorder 5B 2014-04-01 no assertion criteria provided literature only

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