Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003037442 | SCV003441061 | pathogenic | Peroxisome biogenesis disorder 2B | 2023-04-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2137295). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome (PMID: 18712838). This variant is present in population databases (rs267608194, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg276*) in the PEX5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX5 are known to be pathogenic (PMID: 18712838, 21031596). |
| Laboratory for Molecular Medicine, |
RCV004017960 | SCV004847354 | likely pathogenic | Zellweger spectrum disorders | 2023-10-23 | criteria provided, single submitter | clinical testing | The p.Arg276X variant in PEX5 has been identified in the homozygous state in 1 individual with clinical features of Zellweger spectrum disorder (Ebberink 2009 PMID: 18712838). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 2137295) and was absent from large population studies (gnomAD, v.3.1.2).This nonsense variant leads to a premature termination codon at position 276, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the PEX5 gene is an established disease mechanism in autosomal recessive Zellweger spectrum disorder. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Zellweger spectrum disorder. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |