ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.2364_2365del (p.Phe789Cysfs) (rs755716911)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780592 SCV000917990 likely pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2018-04-06 criteria provided, single submitter clinical testing Variant summary: PEX6 c.2364_2365delGT (p.Phe789CysfsX14) 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. The variant allele was found at a frequency of 3.3e-05 in 246072 control chromosomes. This frequency is not higher than expected for a pathogenic variant in PEX6 causing Zellweger Syndrome (3.3e-05 vs 0.0019), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2364_2365delGT in individuals affected with Zellweger Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000780592 SCV001200703 pathogenic Peroxisome biogenesis disorders, Zellweger syndrome spectrum 2019-02-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe789Cysfs*14) in the PEX6 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 poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with PEX6-related conditions. Loss-of-function variants in PEX6 are known to be pathogenic (PMID: 8670792, 19877282, 21031596). For these reasons, this variant has been classified as Pathogenic.

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