ClinVar Genomic variation as it relates to human health
NM_014795.4(ZEB2):c.1027C>T (p.Arg343Ter)
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_014795.4(ZEB2):c.1027C>T (p.Arg343Ter)
Variation ID: 189281 Accession: VCV000189281.24
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q22.3 2: 144400160 (GRCh38) [ NCBI UCSC ] 2: 145157727 (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 Apr 8, 2015 May 1, 2024 Jan 19, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_014795.4:c.1027C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055610.1:p.Arg343Ter nonsense NM_001171653.2:c.955C>T NP_001165124.1:p.Arg319Ter nonsense NC_000002.12:g.144400160G>A NC_000002.11:g.145157727G>A NG_016431.1:g.125232C>T - Protein change
- R343*, R319*
- Other names
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- Canonical SPDI
- NC_000002.12:144400159:G:A
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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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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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ZEB2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1327 | 1396 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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 (7) |
criteria provided, multiple submitters, no conflicts
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Jan 19, 2024 | RCV000169715.19 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 30, 2021 | RCV000723419.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 17, 2021 | RCV001266280.5 |
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
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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
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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
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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
(Feb 23, 2015)
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criteria provided, single submitter
Method: clinical testing
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Mowat-Wilson syndrome
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000249481.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Pathogenic
(May 18, 2014)
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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: SCV000232736.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 6
Sex: mixed
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Pathogenic
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Mowat-Wilson syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002045651.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
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Pathogenic
(Dec 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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Mowat-Wilson syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002050742.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
Variant summary: ZEB2 c.1027C>T (p.Arg343X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: ZEB2 c.1027C>T (p.Arg343X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been reported in affected individuals (HGMD). The variant was absent in 251184 control chromosomes (gnomAD). c.1027C>T has been reported in the literature in multiple individuals affected with Mowat-Wilson Syndrome (examples: Wilson_2003, Ishihara_2004, Yamada_2014, Schuster_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters have assessed this variant after 2014, and all submissions have classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Dec 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Mowat-Wilson syndrome
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV002051772.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Pathogenic
(Nov 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002031008.2
First in ClinVar: Dec 12, 2021 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25525159, 12784289, 31376723, 15384097, 19842203, 24715670, 25608121, 25899569, 16053902) (less)
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Pathogenic
(Jan 19, 2024)
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criteria provided, single submitter
Method: clinical testing
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Mowat-Wilson syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001221054.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg343*) in the ZEB2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg343*) in the ZEB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZEB2 are known to be pathogenic (PMID: 16053902). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Mowat-Wilson syndrome (PMID: 12784289, 15121779, 19842203, 24715670). ClinVar contains an entry for this variant (Variation ID: 189281). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001444453.4
First in ClinVar: Nov 21, 2020 Last updated: May 01, 2024 |
Comment:
The c.1027C>T (p.R343*) alteration, located in exon 8 (coding exon 7) of the ZEB2 gene, consists of a C to T substitution at nucleotide position … (more)
The c.1027C>T (p.R343*) alteration, located in exon 8 (coding exon 7) of the ZEB2 gene, consists of a C to T substitution at nucleotide position 1027. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 343. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD), the ZEB2 c.1027C>T alteration was not observed, with coverage at this position. This alteration has been detected in several individuals with symptoms consistent with Mowat Wilson syndrome (Wilson, 2003; Zweier, 2005; Yamada, 2014; Paz, 2015). An 18 year old male reported by Wilson et al. (2003) had intellectual disability, epilepsy, microcephaly, tetralogy of Fallot, hypospadias, and pelvi-ureteric junction obstruction._x000D_ _x000D_ reminder to manually add internal co-seg data to report Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(Mar 02, 2015)
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no assertion criteria provided
Method: clinical testing
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Mowat-Wilson syndrome
Affected status: yes
Allele origin:
unknown
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Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics
Accession: SCV000221254.1
First in ClinVar: Apr 08, 2015 Last updated: Apr 08, 2015 |
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Pathogenic
(Jan 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Mowat-Wilson syndrome
Affected status: yes
Allele origin:
de novo
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Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV001428403.1
First in ClinVar: Aug 13, 2020 Last updated: Aug 13, 2020 |
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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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Mowat-Wilson syndrome: Generation of two human iPS cell lines (UUIGPi004A and UUIGPi005A) from siblings with a truncating ZEB2 gene variant. | Schuster J | Stem cell research | 2019 | PMID: 31376723 |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Mowat-Wilson syndrome: neurological and molecular study in seven patients. | Paz JA | Arquivos de neuro-psiquiatria | 2015 | PMID: 25608121 |
The spectrum of ZEB2 mutations causing the Mowat-Wilson syndrome in Japanese populations. | Yamada Y | American journal of medical genetics. Part A | 2014 | PMID: 24715670 |
Comprehensive ZEB2 gene analysis for Mowat-Wilson syndrome in a North American cohort: a suggested approach to molecular diagnostics. | Saunders CJ | American journal of medical genetics. Part A | 2009 | PMID: 19842203 |
Mowat-Wilson syndrome. | Garavelli L | Orphanet journal of rare diseases | 2007 | PMID: 17958891 |
Clinical and mutational spectrum of Mowat-Wilson syndrome. | Zweier C | European journal of medical genetics | 2005 | PMID: 16053902 |
Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22-q24.1. | Ishihara N | Journal of medical genetics | 2004 | PMID: 15121779 |
Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B. | Wilson M | American journal of medical genetics. Part A | 2003 | PMID: 12784289 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ZEB2 | - | - | - | - |
Text-mined citations for rs786204815 ...
HelpRecord last updated May 01, 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.