Submissions for variant NM_001127649.3(PEX26):c.228C>T (p.Gly76=)

dbSNP: rs786205556

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
3billion	RCV001808443	SCV002058914	uncertain significance	Peroxisome biogenesis disorder 7A (Zellweger)	2022-01-03	criteria provided, single submitter	clinical testing	The variant has been reported to be associated with PEX26 related disorder (ClinVar ID: VCV000191169, PMID:27124789).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000000, PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001852066	SCV002182093	uncertain significance	Peroxisome biogenesis disorder 7A (Zellweger); Peroxisome biogenesis disorder 7B	2022-08-09	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that this variant results in skipping of 4 nucleotides in the transcript and introduces a premature termination codon (PMID: 32552793). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 191169). This variant has not been reported in the literature in individuals affected with PEX26-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 76 of the PEX26 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PEX26 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.
CeGaT Center for Human Genetics Tuebingen	RCV000171354	SCV003916348	uncertain significance	not provided	2023-01-01	criteria provided, single submitter	clinical testing	PEX26: PM2, PP3, PS3:Supporting
Institute of Human Genetics, Cologne University	RCV001808443	SCV003929418	likely pathogenic	Peroxisome biogenesis disorder 7A (Zellweger)	2022-11-22	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001808443	SCV004804729	uncertain significance	Peroxisome biogenesis disorder 7A (Zellweger)	2024-03-17	criteria provided, single submitter	research
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000171354	SCV000221551	likely pathogenic	not provided		flagged submission	research