ClinVar Genomic variation as it relates to human health
NM_000318.3(PEX2):c.339_345del (p.Gly113_Arg114insTer)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000318.3(PEX2):c.339_345del (p.Gly113_Arg114insTer)
Variation ID: 287499 Accession: VCV000287499.19
- Type and length
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Deletion, 7 bp
- Location
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Cytogenetic: 8q21.13 8: 76983834-76983840 (GRCh38) [ NCBI UCSC ] 8: 77896070-77896076 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2016 Jun 17, 2024 Mar 20, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000318.3:c.339_345del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000309.2:p.Gly113_Arg114insTer frameshift NM_000318.3:c.339_345delCAGGTGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000318.2:c.339_345del NM_001079867.2:c.339_345del NP_001073336.2:p.Gly113_Arg114insTer frameshift NM_001172086.2:c.339_345del NP_001165557.2:p.Gly113_Arg114insTer frameshift NM_001172087.2:c.339_345del NP_001165558.2:p.Gly113_Arg114insTer frameshift NC_000008.11:g.76983839_76983845del NC_000008.10:g.77896075_77896081del NG_008371.1:g.21449_21455del - Protein change
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- Other names
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- Canonical SPDI
- NC_000008.11:76983833:CCACCTGCCACC:CCACC
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PEX2 | - | - |
GRCh38 GRCh37 |
483 | 524 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Mar 20, 2024 | RCV000310327.15 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 26, 2021 | RCV000410454.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 28, 2017 | RCV000587540.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 11, 2016 | RCV000726022.4 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 16, 2020 | RCV001275873.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696557.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The PEX2 c.339_345delCAGGTGG (p.Arg114fs) variant results in a premature termination codon, predicted to cause a truncated or absent PEX2 protein due to nonsense … (more)
Variant summary: The PEX2 c.339_345delCAGGTGG (p.Arg114fs) variant results in a premature termination codon, predicted to cause a truncated or absent PEX2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. LCA has classified another downstream truncation variant, c.355C>T (p.Arg119X) as pathogenic. This variant was found in 3/121458 control chromosomes at a frequency of 0.0000247, which does not exceed the estimated maximal expected allele frequency of a pathogenic PEX2 variant (0.001118). A publication has cited the variant in two individuals, one homozygous and one assumed compound heterozygous, diagnosed with ZS (Ebberink_2010). In addition, multiple clinical diagnostic laboratories classified this variant as "likely pathogenic/pathogenic. Taken together, this variant is classified as "Pathogenic." (less)
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Pathogenic
(Apr 11, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000341287.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder 5A (Zellweger)
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001367739.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5.
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Likely pathogenic
(Aug 16, 2016)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder 5B
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000487610.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Likely pathogenic
(Aug 16, 2016)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder 5A (Zellweger)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000487609.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Oct 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder 5A (Zellweger)
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000963663.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg114*) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg114*) in the PEX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 192 amino acid(s) of the PEX2 protein. This variant is present in population databases (rs764771123, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome (PMID: 21031596). ClinVar contains an entry for this variant (Variation ID: 287499). This variant disrupts a region of the PEX2 protein in which other variant(s) (p.Arg119*) have been determined to be pathogenic (PMID: 1546315, 9452066, 9585609, 10528859). 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. (less)
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Pathogenic
(Oct 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder 5B
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581204.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS4_SUP, PM2_SUP
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Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Feb 01, 2024)
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criteria provided, single submitter
Method: curation
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Peroxisome biogenesis disorder 5A (Zellweger)
Affected status: no
Allele origin:
germline
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Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV005051925.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
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Pathogenic
(Mar 20, 2024)
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criteria provided, single submitter
Method: clinical testing
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Peroxisome biogenesis disorder 5A (Zellweger)
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004201468.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Zellweger syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001461520.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder. | Ebberink MS | Human mutation | 2011 | PMID: 21031596 |
Defective PEX gene products correlate with the protein import, biochemical abnormalities, and phenotypic heterogeneity in peroxisome biogenesis disorders. | Shimozawa N | Journal of medical genetics | 1999 | PMID: 10528859 |
Temperature-sensitive phenotypes of peroxisome-assembly processes represent the milder forms of human peroxisome-biogenesis disorders. | Imamura A | American journal of human genetics | 1998 | PMID: 9585609 |
A novel mutation, R125X in peroxisome assembly factor-1 responsible for Zellweger syndrome. | Shimozawa N | Human mutation | 1998 | PMID: 9452066 |
A human gene responsible for Zellweger syndrome that affects peroxisome assembly. | Shimozawa N | Science (New York, N.Y.) | 1992 | PMID: 1546315 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PEX2 | - | - | - | - |
Text-mined citations for rs764771123 ...
HelpRecord last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.