Submissions for variant NM_001127649.3(PEX26):c.200A>G (p.Asn67Ser)

gnomAD frequency: 0.00179  dbSNP: rs201884779

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726167	SCV000342571	uncertain significance	not provided	2017-09-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000338698	SCV000437328	uncertain significance	Peroxisome biogenesis disorder 7A (Zellweger)	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000726167	SCV000583142	uncertain significance	not provided	2017-05-25	criteria provided, single submitter	clinical testing	The N67S variant in the PEX26 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 75/25,018 alleles (0.3%) from individuals of non-Finnish European background in the ExAC dataset, with no homozygous control individuals reported (Lek et al., 2016). The N67S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. As there is not enough information currently available to determine if this variant is pathogenic or benign, we interpret N67S as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV000765604	SCV000896927	uncertain significance	Peroxisome biogenesis disorder 7A (Zellweger); Peroxisome biogenesis disorder 7B	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000765604	SCV001107521	likely benign	Peroxisome biogenesis disorder 7A (Zellweger); Peroxisome biogenesis disorder 7B	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000726167	SCV004152072	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	PEX26: BP4
PreventionGenetics, part of Exact Sciences	RCV003930152	SCV004746441	likely benign	PEX26-related condition	2022-02-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).