ClinVar Miner

Submissions for variant NM_000288.4(PEX7):c.694C>T (p.Arg232Ter) (rs121909153)

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Total submissions: 6
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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 2020-03-04 criteria provided, single submitter clinical testing 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. This variant is present in population databases (rs121909153, ExAC 0.006%). This variant has been observed in individual(s) with rhizomelic chondrodysplasia punctata (PMID: 10083738, 26587300). ClinVar contains an entry for this variant (Variation ID: 7783). Loss-of-function variants in PEX7 are known to be pathogenic (PMID: 12325024, 12522768, 20301447). For these reasons, this variant has been classified as Pathogenic.
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.
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

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