Submissions for variant NM_000318.3(PEX2):c.550del (p.Cys184fs)

dbSNP: rs63545361

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000794931	SCV000934368	pathogenic	Peroxisome biogenesis disorder 5A (Zellweger)	2022-05-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg184Valfs*8) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 122 amino acid(s) of the PEX2 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the PEX2 protein. Other variant(s) that disrupt this region (p.Trp223*, p.Phe278Leufs*3) have been observed in individuals with PEX2-related conditions (PMID: 14630978, 17041890). This suggests that this may be a clinically significant region of the protein. Experimental studies have shown that this premature translational stop signal affects PEX2 function (PMID: 10652207). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This premature translational stop signal has been observed in individual(s) with peroxisomal biogenesis disorder (PBD) (PMID: 10652207). This variant is not present in population databases (gnomAD no frequency).
Genetics Institute, Tel Aviv Sourasky Medical Center	RCV001391252	SCV001593201	pathogenic	Zellweger spectrum disorders	2021-05-12	criteria provided, single submitter	clinical testing