ClinVar Miner

Submissions for variant NM_000288.4(PEX7):c.13_19dup (p.Gly7fs) (rs62636519)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411594 SCV000485994 likely pathogenic Rhizomelic chondrodysplasia punctata type 1 2016-03-14 criteria provided, single submitter clinical testing
Invitae RCV000008232 SCV000937306 pathogenic Peroxisome biogenesis disorder 9B 2019-08-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly7Valfs*51) in the PEX7 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 insufficient coverage at this position in the ExAC database. This variant has been observed in an individual affected with Refsum disease (PMID: 12522768). ClinVar contains an entry for this variant (Variation ID: 370629). Loss-of-function variants in PEX7 are known to be pathogenic (PMID: 12325024, 20301447). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000411594 SCV001162990 pathogenic Rhizomelic chondrodysplasia punctata type 1 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000411594 SCV001983448 pathogenic Rhizomelic chondrodysplasia punctata type 1 2021-09-13 criteria provided, single submitter clinical testing Variant summary: PEX7 c.13_19dupTGCGGTG (p.Gly7ValfsX51) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8.1e-06 in 124026 control chromosomes. c.13_19dupTGCGGTG has been reported in the literature as a compound heterozygous genotype in at-least one individual affected with Refsum disease (Rhizomelic Chondrodysplasia Punctata Type 1) and has been subsequently cited by others (example, van den Brink_2003, Jansen_2004, Nanetti_2015). To our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported, although the reported compound heterozygous patient had defects not only in phytanic acid alpha-oxidation but also in plasmalogen synthesis and peroxisomal thiolase. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000008232 SCV000028439 pathogenic Peroxisome biogenesis disorder 9B 2003-02-01 no assertion criteria provided literature only
GeneReviews RCV000411594 SCV000055655 pathologic Rhizomelic chondrodysplasia punctata type 1 2012-09-13 no assertion criteria provided curation Converted during submission to Pathogenic.

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