ClinVar Miner

Submissions for variant NM_002617.4(PEX10):c.704dup (p.Leu236fs)

gnomAD frequency: 0.00008  dbSNP: rs61750435
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000324305 SCV000329456 pathogenic not provided 2020-10-20 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation as the last 91 amino acids are replaced with 102 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 21031596, 10862081, 17702006, 20695019)
Counsyl RCV000007176 SCV000487553 pathogenic Peroxisome biogenesis disorder 6A (Zellweger) 2016-07-22 criteria provided, single submitter clinical testing
Counsyl RCV000149808 SCV000487554 pathogenic Peroxisome biogenesis disorder 6B 2016-07-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000644606 SCV000766306 pathogenic Peroxisome biogenesis disorder, complementation group 7 2024-11-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu256Alafs*103) in the PEX10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 91 amino acid(s) of the PEX10 protein. This variant is present in population databases (rs61750435, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with Zellweger syndrome spectrum (PMID: 10862081, 17702006, 19105186, 20695019, 21031596). This variant is also known as c.704dupA, c.764_765insA or p.L256fsX102. ClinVar contains an entry for this variant (Variation ID: 6774). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects PEX10 function (PMID: 10862081, 20695019). For these reasons, this variant has been classified as Pathogenic.
Eurofins Ntd Llc (ga) RCV000324305 SCV000858406 pathogenic not provided 2017-11-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781707 SCV000919970 pathogenic Peroxisome biogenesis disorder 2017-09-14 criteria provided, single submitter clinical testing Variant summary: The PEX10 c.764dupA (p.Leu256AlafsX92+) variant causes a frameshift and is predicted to result in an elongation of the protein. One frameshift/elongation variant in PEX10 has been classified as pathogenic by our laboratory (e.g. c.874_875delCT, p.Leu292fsX55+). One in silico tool predicts a damaging outcome for this variant. One functional study showed less than 50% relative rescue activity compared to the wild type (Warren_2000). The variant was found in the control population dataset of ExAC in 2/93566 control chromosomes at a frequency of 0.0000214, which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX10 variant (0.001118). This variant was reported in multiple Zellweger syndrome patients, in homozygotes and heterozygotes, including one case of uniparental disomy (Ebberink_2010, Turner_PEX10). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Baylor Genetics RCV000007176 SCV004203406 pathogenic Peroxisome biogenesis disorder 6A (Zellweger) 2024-03-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005007833 SCV005641559 pathogenic Peroxisome biogenesis disorder 6A (Zellweger); Peroxisome biogenesis disorder 6B 2024-02-06 criteria provided, single submitter clinical testing
OMIM RCV000007176 SCV000027372 pathogenic Peroxisome biogenesis disorder 6A (Zellweger) 2010-08-01 no assertion criteria provided literature only
OMIM RCV000149808 SCV000196632 pathogenic Peroxisome biogenesis disorder 6B 2010-08-01 no assertion criteria provided literature only
Natera, Inc. RCV001273135 SCV001455740 pathogenic Zellweger spectrum disorders 2020-09-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004751207 SCV005360214 pathogenic PEX10-related disorder 2024-06-05 no assertion criteria provided clinical testing The PEX10 c.764dupA variant is predicted to result in a frameshift and premature protein termination (p.Leu256Alafs*103). This variant was found in a compound heterozygous state in three patients affected by peroxisomal biogenesis disorders (PBD) (Warren et al. 2000. PubMed ID: 10862081; Steinberg et al. 2004. PubMed ID: 15542397; Régal et al. 2010. PubMed ID: 20695019). This variant is reported in 0.0056% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in PEX10 are expected to be pathogenic. This variant is interpreted as pathogenic.

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