ClinVar Miner

Submissions for variant NM_000288.4(PEX7):c.345T>G (p.Tyr115Ter)

gnomAD frequency: 0.00001  dbSNP: rs121909154
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411170 SCV000486131 likely pathogenic Rhizomelic chondrodysplasia punctata type 1 2016-04-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000411170 SCV000919982 pathogenic Rhizomelic chondrodysplasia punctata type 1 2018-05-24 criteria provided, single submitter clinical testing Variant summary: PEX7 c.345T>G (p.Tyr115X) 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. One functional study confirmed that this variant is triggering nonsense-mediated decay with lack of a full length transcript (Braverman_2002). The variant allele was found at a frequency of 4.1e-05 in 246196 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in PEX7 causing Rhizomelic Chondrodysplasia Punctata Type 1 (4.1e-05 vs 1.90e-03), allowing no conclusion about variant significance. The variant, c.345T>G, has been reported in the literature in individuals affected with Rhizomelic Chondrodysplasia Punctata Type 1 (Motley_PEX7_AMJHumGenet_2002) and the subphenotype adult Refsum disease (ARD) when found in compound heterozygosity with IVS3-10A>G (Braverman_2002). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classifies the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000008228 SCV001388016 pathogenic Peroxisome biogenesis disorder 9B 2021-08-24 criteria provided, single submitter clinical testing
OMIM RCV000008228 SCV000028435 pathogenic Peroxisome biogenesis disorder 9B 2007-02-27 no assertion criteria provided literature only
Natera, Inc. RCV001826453 SCV002077240 pathogenic Rhizomelic chondrodysplasia punctata 2020-11-19 no assertion criteria provided clinical testing

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