NM_000318.3(PEX2):c.220dup (p.Ala74fs) AND Peroxisome biogenesis disorder 5A (Zellweger)

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 11, 2022
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:: RCV001953126.4

Allele description [Variation Report for NM_000318.3(PEX2):c.220dup (p.Ala74fs)]

NM_000318.3(PEX2):c.220dup (p.Ala74fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

8q21.13

Genomic location:

Preferred name:

NM_000318.3(PEX2):c.220dup (p.Ala74fs)

HGVS:

NC_000008.11:g.76983959dup
NG_008371.1:g.21330dup
NM_000318.3:c.220dupMANE SELECT
NM_001079867.2:c.220dup
NM_001172086.2:c.220dup
NM_001172087.2:c.220dup
NP_000309.2:p.Ala74fs
NP_001073336.2:p.Ala74fs
NP_001165557.2:p.Ala74fs
NP_001165558.2:p.Ala74fs
NC_000008.10:g.77896194_77896195insC
NC_000008.10:g.77896195dup

Protein change:

A74fs

Links:

dbSNP: rs777974798

NCBI 1000 Genomes Browser:

rs777974798

Molecular consequence:

NM_000318.3:c.220dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079867.2:c.220dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001172086.2:c.220dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001172087.2:c.220dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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Klebsiella pneumoniae strain WCHKP040017, whole genome shotgun sequencing projec...
Klebsiella pneumoniae strain WCHKP040017, whole genome shotgun sequencing project
gi|1374942365|gb|PWDL00000000.1|PWD 0000

Nucleotide
Klebsiella pneumoniae subsp. pneumoniae strain WCHKP015095, whole genome shotgun...
Klebsiella pneumoniae subsp. pneumoniae strain WCHKP015095, whole genome shotgun sequencing project
gi|1318858694|gb|NWDB00000000.1|NWD 0000

Nucleotide
Klebsiella pneumoniae strain WCHKP020109, whole genome shotgun sequencing projec...
Klebsiella pneumoniae strain WCHKP020109, whole genome shotgun sequencing project
gi|1374941836|gb|PWDA00000000.1|PWD 0000

Nucleotide
Klebsiella pneumoniae strain WCHKP7J8, whole genome shotgun sequencing project
Klebsiella pneumoniae strain WCHKP7J8, whole genome shotgun sequencing project
gi|1233270863|gb|NBXW00000000.1|NBX 0000

Nucleotide
Klebsiella pneumoniae strain WCHKP040043, whole genome shotgun sequencing projec...
Klebsiella pneumoniae strain WCHKP040043, whole genome shotgun sequencing project
gi|1374915912|gb|PWBC00000000.1|PWB 0000

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002220560	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2022)	germline	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

SCV002220560

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 11, 2022)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV002220560.3

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

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.Leu207Serfs*10) have been determined to be pathogenic (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 present in population databases (rs777974798, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Ala74Glyfs*11) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 232 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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