NM_000318.3(PEX2):c.232C>T (p.Gln78Ter) AND Peroxisome biogenesis disorder 5A (Zellweger)

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Sep 5, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000805043.8

Allele description [Variation Report for NM_000318.3(PEX2):c.232C>T (p.Gln78Ter)]

NM_000318.3(PEX2):c.232C>T (p.Gln78Ter)

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.232C>T (p.Gln78Ter)

HGVS:

NC_000008.11:g.76983947G>A
NG_008371.1:g.21342C>T
NM_000318.3:c.232C>TMANE SELECT
NM_001079867.2:c.232C>T
NM_001172086.2:c.232C>T
NM_001172087.2:c.232C>T
NP_000309.2:p.Gln78Ter
NP_001073336.2:p.Gln78Ter
NP_001165557.2:p.Gln78Ter
NP_001165558.2:p.Gln78Ter
NC_000008.10:g.77896183G>A
NM_000318.2:c.232C>T

Protein change:

Q78*

Links:

dbSNP: rs1586070043

NCBI 1000 Genomes Browser:

rs1586070043

Molecular consequence:

NM_000318.3:c.232C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001079867.2:c.232C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001172086.2:c.232C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001172087.2:c.232C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Peroxisome biogenesis disorder 5A (Zellweger) (PBD5A)
Identifiers:: MONDO: MONDO:0013932; MedGen: C3553940; Orphanet: 912; OMIM: 614866

Recent activity

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60S ribosomal protein L23 [Juglans regia]
60S ribosomal protein L23 [Juglans regia]
gi|1882614556|ref|XP_035548350.1|

Protein
Chain A, Microcephalin
Chain A, Microcephalin
gi|358439821|pdb|3SZM|A

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000944985	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 4, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 1546315, 7681622, 9452066, 9585609, 10528859, 15542397, 21465523, 23430938, 28492532
SCV004201474	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 5, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000944985

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 4, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV004201474

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 5, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

A human gene responsible for Zellweger syndrome that affects peroxisome assembly.

Shimozawa N, Tsukamoto T, Suzuki Y, Orii T, Shirayoshi Y, Mori T, Fujiki Y.

Science. 1992 Feb 28;255(5048):1132-4.

PubMed [citation]

PMID:: 1546315

Standardization of complementation grouping of peroxisome-deficient disorders and the second Zellweger patient with peroxisomal assembly factor-1 (PAF-1) defect.

Shimozawa N, Suzuki Y, Orii T, Moser A, Moser HW, Wanders RJ.

Am J Hum Genet. 1993 Apr;52(4):843-4. No abstract available.

PubMed [citation]

PMID:: 7681622
PMCID:: PMC1682069

See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000944985.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change creates a premature translational stop signal (p.Gln78*) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 228 amino acid(s) of the PEX2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PEX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 649982). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the PEX2 protein in which other variant(s) (p.Arg119*) have been determined to be pathogenic (PMID: 1546315, 7681622, 9452066, 9585609, 10528859, 15542397, 21465523, 23430938). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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

From Baylor Genetics, SCV004201474.1

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

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

Last Updated: Sep 29, 2024

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