Submissions for variant NM_000318.3(PEX2):c.339_345del (p.Gly113_Arg114insTer)

dbSNP: rs764771123

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726022	SCV000341287	pathogenic	not provided	2016-04-11	criteria provided, single submitter	clinical testing
Counsyl	RCV000310327	SCV000487609	likely pathogenic	Peroxisome biogenesis disorder 5A (Zellweger)	2016-08-16	criteria provided, single submitter	clinical testing
Counsyl	RCV000410454	SCV000487610	likely pathogenic	Peroxisome biogenesis disorder 5B	2016-08-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587540	SCV000696557	pathogenic	Peroxisome biogenesis disorder	2017-04-28	criteria provided, single submitter	clinical testing	Variant summary: The PEX2 c.339_345delCAGGTGG (p.Arg114fs) variant results in a premature termination codon, predicted to cause a truncated or absent PEX2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. LCA has classified another downstream truncation variant, c.355C>T (p.Arg119X) as pathogenic. This variant was found in 3/121458 control chromosomes at a frequency of 0.0000247, which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX2 variant (0.001118). A publication has cited the variant in two individuals, one homozygous and one assumed compound heterozygous, diagnosed with ZS (Ebberink_2010). In addition, multiple clinical diagnostic laboratories classified this variant as "likely pathogenic/pathogenic. Taken together, this variant is classified as "Pathogenic."
Invitae	RCV000310327	SCV000963663	pathogenic	Peroxisome biogenesis disorder 5A (Zellweger)	2023-10-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg114*) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 192 amino acid(s) of the PEX2 protein. This variant is present in population databases (rs764771123, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome (PMID: 21031596). ClinVar contains an entry for this variant (Variation ID: 287499). This variant disrupts a region of the PEX2 protein in which other variant(s) (p.Arg119*) have been determined to be pathogenic (PMID: 1546315, 9452066, 9585609, 10528859). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000310327	SCV001367739	pathogenic	Peroxisome biogenesis disorder 5A (Zellweger)	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5.
MGZ Medical Genetics Center	RCV000410454	SCV002581204	pathogenic	Peroxisome biogenesis disorder 5B	2021-10-26	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000310327	SCV004201468	pathogenic	Peroxisome biogenesis disorder 5A (Zellweger)	2023-10-03	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001275873	SCV001461520	pathogenic	Zellweger spectrum disorders	2020-09-16	no assertion criteria provided	clinical testing