NM_000318.3(PEX2):c.163G>A (p.Glu55Lys) AND Peroxisome biogenesis disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 27, 2023
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:: RCV003323360.2

Allele description [Variation Report for NM_000318.3(PEX2):c.163G>A (p.Glu55Lys)]

NM_000318.3(PEX2):c.163G>A (p.Glu55Lys)

Gene:

PEX2:peroxisomal biogenesis factor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.13

Genomic location:

Preferred name:

NM_000318.3(PEX2):c.163G>A (p.Glu55Lys)

HGVS:

NC_000008.11:g.76984016C>T
NG_008371.1:g.21273G>A
NM_000318.2:c.163G>A
NM_000318.3:c.163G>AMANE SELECT
NM_001079867.2:c.163G>A
NM_001172086.2:c.163G>A
NM_001172087.2:c.163G>A
NP_000309.2:p.Glu55Lys
NP_001073336.2:p.Glu55Lys
NP_001165557.2:p.Glu55Lys
NP_001165558.2:p.Glu55Lys
NC_000008.10:g.77896252C>T
P28328:p.Glu55Lys

Protein change:

E55K; GLU55LYS

Links:

UniProtKB: P28328#VAR_011389; OMIM: 170993.0002; dbSNP: rs61752119

NCBI 1000 Genomes Browser:

rs61752119

Molecular consequence:

NM_000318.3:c.163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001079867.2:c.163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001172086.2:c.163G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001172087.2:c.163G>A - 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
SCV004028599	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jul 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9585609, 10528859, 10960480 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004028599

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jul 27, 2023)

germline

clinical testing

PubMed (3)
[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

Temperature-sensitive phenotypes of peroxisome-assembly processes represent the milder forms of human peroxisome-biogenesis disorders.

Imamura A, Tsukamoto T, Shimozawa N, Suzuki Y, Zhang Z, Imanaka T, Fujiki Y, Orii T, Kondo N, Osumi T.

Am J Hum Genet. 1998 Jun;62(6):1539-43. No abstract available.

PubMed [citation]

PMID:: 9585609
PMCID:: PMC1377160

Defective PEX gene products correlate with the protein import, biochemical abnormalities, and phenotypic heterogeneity in peroxisome biogenesis disorders.

Shimozawa N, Imamura A, Zhang Z, Suzuki Y, Orii T, Tsukamoto T, Osumi T, Fujiki Y, Wanders RJ, Besley G, Kondo N.

J Med Genet. 1999 Oct;36(10):779-81.

PubMed [citation]

PMID:: 10528859
PMCID:: PMC1734244

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004028599.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: PEX2 c.163G>A (p.Glu55Lys) results in a conservative amino acid change to a highly conserved residue (HGMD) located in the Pex, N-terminal (IPR006845) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251214 control chromosomes (gnomAD). c.163G>A has been reported in the literature in an individual affected with Refsum disease who was compound heterozygous with a pathogenic variant (Imamura_1998, Shimozawa_1999). These data suggest the variant may be associated with disease. At least two publications report experimental evidence evaluating an impact on protein function, finding that cells expressing the variant protein showed partially reduced enzymatic activity and recapitulated the catalase-less persoxisomes seen in patient cells (Fujiwara_2000, Shimozawa_1999). The following publications have been ascertained in the context of this evaluation (PMID: 9585609, 10528859, 10960480). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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: Sep 3, 2023

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