NM_001127649.3(PEX26):c.292C>T (p.Arg98Trp) AND Peroxisome biogenesis disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 14, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000780589.1

Allele description [Variation Report for NM_001127649.3(PEX26):c.292C>T (p.Arg98Trp)]

NM_001127649.3(PEX26):c.292C>T (p.Arg98Trp)

Gene:

PEX26:peroxisomal biogenesis factor 26 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_001127649.3(PEX26):c.292C>T (p.Arg98Trp)

HGVS:

NC_000022.11:g.18079935C>T
NG_008339.1:g.7016C>T
NM_001127649.3:c.292C>TMANE SELECT
NM_001199319.2:c.292C>T
NM_017929.6:c.292C>T
NP_001121121.1:p.Arg98Trp
NP_001186248.1:p.Arg98Trp
NP_060399.1:p.Arg98Trp
NC_000022.10:g.18562701C>T
NM_017929.5:c.292C>T
NM_017929.6:c.292C>T
Q7Z412:p.Arg98Trp

Protein change:

R98W; ARG98TRP

Links:

UniProtKB: Q7Z412#VAR_018649; OMIM: 608666.0001; dbSNP: rs62641228

NCBI 1000 Genomes Browser:

rs62641228

Molecular consequence:

NM_001127649.3:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001199319.2:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_017929.6:c.292C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Peroxisome biogenesis disorder (PBD, ZSS)
Synonyms:: PEROXISOME BIOGENESIS DISORDER (NEONATAL ADRENOLEUKODYSTROPHY/INFANTILE REFSUM DISEASE); INFANTILE PHYTANIC ACID STORAGE DISEASE; PEROXISOME BIOGENESIS DISORDER (NALD/IRD); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019234; MedGen: C1832200; OMIM: PS214100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000917986	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 14, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19877282, 16257970 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000917986

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Sep 14, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients.

Ebberink MS, Kofster J, Wanders RJ, Waterham HR.

Hum Mutat. 2010 Jan;31(1):E1058-70. doi: 10.1002/humu.21153.

PubMed [citation]

PMID:: 19877282

Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with the Pex1p x Pex6p complex.

Furuki S, Tamura S, Matsumoto N, Miyata N, Moser A, Moser HW, Fujiki Y.

J Biol Chem. 2006 Jan 20;281(3):1317-23. Epub 2005 Oct 27.

PubMed [citation]

PMID:: 16257970

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917986.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: PEX26 c.292C>T (p.Arg98Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.5e-05 in 277208 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in PEX26 causing Zellweger Syndrome (6.5e-05 vs 0.0016), allowing no conclusion about variant significance. c.292C>T has been reported in the literature in multiple individuals affected with Zellweger Syndrome (Ebberink_2010). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in between 50%-90% of normal activity (Furuki_2006). A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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