NM_000318.3(PEX2):c.320_326del (p.Ala107fs) AND Peroxisome biogenesis disorder 5A (Zellweger)

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 28, 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:: RCV003649622.1

Allele description [Variation Report for NM_000318.3(PEX2):c.320_326del (p.Ala107fs)]

NM_000318.3(PEX2):c.320_326del (p.Ala107fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

8q21.13

Genomic location:

Preferred name:

NM_000318.3(PEX2):c.320_326del (p.Ala107fs)

HGVS:

NC_000008.11:g.76983855_76983861del
NG_008371.1:g.21430_21436del
NG_008371.2:g.22185_22191del
NM_000318.3:c.320_326delMANE SELECT
NM_001079867.2:c.320_326del
NM_001172086.2:c.320_326del
NM_001172087.2:c.320_326del
NP_000309.2:p.Ala107fs
NP_001073336.2:p.Ala107fs
NP_001165557.2:p.Ala107fs
NP_001165558.2:p.Ala107fs
NC_000008.10:g.77896089_77896095del
NC_000008.10:g.77896091_77896097del

Protein change:

A107fs

Molecular consequence:

NM_000318.3:c.320_326del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079867.2:c.320_326del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001172086.2:c.320_326del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001172087.2:c.320_326del - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004395141	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 28, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 1546315, 7681622, 9452066, 9585609, 10528859, 15542397, 21465523, 23430938, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004395141

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 28, 2023)

germline

clinical testing

PubMed (9)
[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

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 (9)

Details of each submission

From Invitae, SCV004395141.1

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

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.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. This variant has not been reported in the literature in individuals affected with PEX2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala107Valfs*8) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 199 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: Feb 28, 2024

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