ClinVar Miner

Submissions for variant NM_017929.6(PEX26):c.34dup (p.Leu12fs) (rs61752129)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727235 SCV000706843 pathogenic not provided 2017-03-07 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000002237 SCV000784352 pathogenic Peroxisome biogenesis disorder 7A 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000662021 SCV000784353 pathogenic Peroxisome biogenesis disorder 7B 2018-03-05 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000002237 SCV000891762 pathogenic Peroxisome biogenesis disorder 7A 2018-11-27 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000780590 SCV000917987 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2018-10-04 criteria provided, single submitter clinical testing Variant summary: PEX26 c.34dupC (p.Leu12ProfsX103) 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 3.9e-05 in 206458 control chromosomes (gnomAD). c.34dupC has been reported in the literature in individuals affected with Zellweger Syndrome (Ebberink 2010, Matsumoto 2003). These data indicate that the variant is likely to be associated with disease. Functional studies indicate the variant impedes peroxisomal localization, catalase import, stability and binding to the Pex6p and Pex1p proteins (Furuki 2006). Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000821185 SCV000961934 pathogenic Peroxisome biogenesis disorder 7A; Peroxisome biogenesis disorder 7B 2018-12-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu12Profs*103) in the PEX26 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual affected with Zellweger syndrome (PMID: 12851857). This variant is also known as T35insC in the literature. ClinVar contains an entry for this variant (Variation ID: 2154). Experimental studies have shown that this nonsense change disrupts PEX26 protein function (PMID: 12851857, 16257970). Loss-of-function variants in PEX26 are known to be pathogenic (PMID: 12851857, 21031596). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002237 SCV000022395 pathogenic Peroxisome biogenesis disorder 7A 2003-08-01 no assertion criteria provided literature only

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