ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2922del (p.Leu974fs)

dbSNP: rs762324548
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478887 SCV000572331 pathogenic not provided 2020-10-05 criteria provided, single submitter clinical testing Frameshift 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); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001376561 SCV001222508 pathogenic Zellweger spectrum disorders 2025-02-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu974Phefs*15) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 21031596, 26387595, 31831025). This variant is present in population databases (rs762324548, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 371696). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003418086 SCV004113961 likely pathogenic PEX1-related disorder 2023-07-18 criteria provided, single submitter clinical testing The PEX1 c.2922delA variant is predicted to result in a frameshift and premature protein termination (p.Leu974Phefs*15). To our knowledge, this variant has not been previously reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-92123804-GT-G). Frameshift variants in PEX1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003993945 SCV004813605 pathogenic Peroxisome biogenesis disorder 2024-02-15 criteria provided, single submitter clinical testing Variant summary: PEX1 c.2922delA (p.Leu974PhefsX15) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 4e-06 in 251324 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2922delA in individuals affected with Zellweger Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 371696). Based on the evidence outlined above, the variant was classified as pathogenic.
Counsyl RCV000411605 SCV000487468 likely pathogenic Peroxisome biogenesis disorder 1A (Zellweger) 2015-12-22 no assertion criteria provided clinical testing
Counsyl RCV000409154 SCV000487469 likely pathogenic Heimler syndrome 1 2015-12-22 no assertion criteria provided clinical testing

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