ClinVar Miner

Submissions for variant NM_000288.4(PEX7):c.694C>T (p.Arg232Ter)

dbSNP: rs121909153
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255604 SCV000322290 pathogenic not provided 2021-02-08 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 10083738, 21465523, 11781871, 12325024, 25525159, 26587300)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000008225 SCV000919980 pathogenic Rhizomelic chondrodysplasia punctata type 1 2018-01-18 criteria provided, single submitter clinical testing Variant summary: The PEX7 c.694C>T (p.Arg232X) variant results in a premature termination codon, predicted to cause a truncated or absent PEX7 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation downstream of this position, c.875T>A (p.Leu292X) has been classified as pathogenic by our laboratory. This variant was found in 1/246228 control chromosomes (gnomAD) at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX7 variant (0.0018708). Multiple publications have cited the variant in affected compound heterozygote and homozygote RCDP1 patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV001064035 SCV001228908 pathogenic Peroxisome biogenesis disorder 9B 2023-08-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg232*) in the PEX7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX7 are known to be pathogenic (PMID: 12325024, 12522768, 20301447). This variant is present in population databases (rs121909153, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with rhizomelic chondrodysplasia punctata (PMID: 10083738, 26587300). ClinVar contains an entry for this variant (Variation ID: 7783).
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001064035 SCV001369103 pathogenic Peroxisome biogenesis disorder 9B 2019-06-22 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP3,PP5.
Baylor Genetics RCV001064035 SCV004201632 pathogenic Peroxisome biogenesis disorder 9B 2023-10-18 criteria provided, single submitter clinical testing
OMIM RCV000008225 SCV000028432 pathogenic Rhizomelic chondrodysplasia punctata type 1 1999-01-01 no assertion criteria provided literature only
Counsyl RCV000008225 SCV000485677 likely pathogenic Rhizomelic chondrodysplasia punctata type 1 2016-01-27 no assertion criteria provided clinical testing
Natera, Inc. RCV001826452 SCV002077251 pathogenic Rhizomelic chondrodysplasia punctata 2020-08-07 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.