NM_000318.3(PEX2):c.386T>A (p.Leu129Ter) AND Peroxisome biogenesis disorder 5A (Zellweger)

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 14, 2021
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:: RCV001950406.4

Allele description [Variation Report for NM_000318.3(PEX2):c.386T>A (p.Leu129Ter)]

NM_000318.3(PEX2):c.386T>A (p.Leu129Ter)

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.386T>A (p.Leu129Ter)

HGVS:

NC_000008.11:g.76983793A>T
NG_008371.1:g.21496T>A
NM_000318.3:c.386T>AMANE SELECT
NM_001079867.2:c.386T>A
NM_001172086.2:c.386T>A
NM_001172087.2:c.386T>A
NP_000309.2:p.Leu129Ter
NP_001073336.2:p.Leu129Ter
NP_001165557.2:p.Leu129Ter
NP_001165558.2:p.Leu129Ter
NC_000008.10:g.77896029A>T

Protein change:

L129*

Links:

dbSNP: rs1224224276

NCBI 1000 Genomes Browser:

rs1224224276

Molecular consequence:

NM_000318.3:c.386T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001079867.2:c.386T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001172086.2:c.386T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001172087.2:c.386T>A - 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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Homo sapiens coiled-coil domain containing 71 (CCDC71), mRNA
Homo sapiens coiled-coil domain containing 71 (CCDC71), mRNA
gi|33285012|ref|NM_022903.2|

Nucleotide
N-terminal EF-hand calcium-binding protein 3 isoform 2 [Homo sapiens]
N-terminal EF-hand calcium-binding protein 3 isoform 2 [Homo sapiens]
gi|149158723|ref|NP_112509.3|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002225666	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10652207, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002225666

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2021)

germline

clinical testing

PubMed (2)
[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

Citations

PubMed

Molecular mechanism of detectable catalase-containing particles, peroxisomes, in fibroblasts from a PEX2-defective patient.

Shimozawa N, Zhang Z, Imamura A, Suzuki Y, Fujiki Y, Tsukamoto T, Osumi T, Aubourg P, Wanders RJ, Kondo N.

Biochem Biophys Res Commun. 2000 Feb 5;268(1):31-5.

PubMed [citation]

PMID:: 10652207

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002225666.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PEX2 protein in which other variant(s) (p.Lys215Serfs*2) have been determined to be pathogenic (PMID: 10652207; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with PEX2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu129*) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 177 amino acid(s) of the PEX2 protein.

#	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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