NM_000288.4(PEX7):c.45_52dup (p.His18fs) AND Peroxisome biogenesis disorder 9B

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 15, 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:: RCV000032589.10

Allele description [Variation Report for NM_000288.4(PEX7):c.45_52dup (p.His18fs)]

NM_000288.4(PEX7):c.45_52dup (p.His18fs)

Gene:

PEX7:peroxisomal biogenesis factor 7 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

6q23.3

Genomic location:

Preferred name:

NM_000288.4(PEX7):c.45_52dup (p.His18fs)

HGVS:

NC_000006.12:g.136822710_136822717dup
NG_008462.1:g.5131_5138dup
NM_000288.4:c.45_52dupMANE SELECT
NP_000279.1:p.His18fs
NC_000006.11:g.137143840_137143841insGGACGCCG
NC_000006.11:g.137143848_137143855dup
NM_000288.3:c.45_52dupGGGACGCC

Protein change:

H18fs

Links:

OMIM: 601757.0005; dbSNP: rs63535662

NCBI 1000 Genomes Browser:

rs63535662

Molecular consequence:

NM_000288.4:c.45_52dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Peroxisome biogenesis disorder 9B
Synonyms:: PEROXISOME BIOGENESIS DISORDER, PEX7-RELATED, ATYPICAL; Refsum disease, adult, 2
Identifiers:: MONDO: MONDO:0013945; MedGen: C2749346; Orphanet: 773; OMIM: 614879

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Homo sapiens misato mitochondrial distribution and morphology regulator 1 (MSTO1...
Homo sapiens misato mitochondrial distribution and morphology regulator 1 (MSTO1), transcript variant 20, mRNA
gi|1184725740|ref|NM_001350784.1|

Nucleotide
Chain F, Histone H4
Chain F, Histone H4
gi|2563387946|pdb|8PEP|F

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000028433	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2002)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000959105	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12325024, 12522768, 20301447, 11781871, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000028433

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 2002)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000959105

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 15, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype.

Braverman N, Chen L, Lin P, Obie C, Steel G, Douglas P, Chakraborty PK, Clarke JT, Boneh A, Moser A, Moser H, Valle D.

Hum Mutat. 2002 Oct;20(4):284-97.

PubMed [citation]

PMID:: 12325024

Identification of PEX7 as the second gene involved in Refsum disease.

van den Brink DM, Brites P, Haasjes J, Wierzbicki AS, Mitchell J, Lambert-Hamill M, de Belleroche J, Jansen GA, Waterham HR, Wanders RJ.

Am J Hum Genet. 2003 Feb;72(2):471-7. Epub 2003 Jan 9.

PubMed [citation]

PMID:: 12522768
PMCID:: PMC379239

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000028433.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 patients with a mild chondrodysplasia punctata phenotype with no rhizomelia (PBD9B; 614879), one from a Swiss family and the other from a French, Motley et al. (2002) detected homozygosity for an 8-nucleotide duplication of nucleotides 45-52 in the PEX7 cDNA (52dupGGGACGCC), predicted to result in frameshift at codon 17 in exon 1 of the PEX7 gene. Coexpression of the 8-bp dup allele with PTS2-tagged GFP in skin fibroblasts from a patient homozygous for a PEX7 null mutation resulted in partial restoration of PTS2-mediated peroxisomal protein import. Although the mutation was predicted to lead to absence of functional peroxin-7, the in vitro results suggested that frame restoration occurs.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000959105.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.His18Argfs*35) in the PEX7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX7 are known to be pathogenic (PMID: 12325024, 12522768, 20301447). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with rhizomelic chondrodysplasia punctata (PMID: 11781871). ClinVar contains an entry for this variant (Variation ID: 7784). For these reasons, this variant has been 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: Sep 29, 2024

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