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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29093530, 25525159, 19842203, 24715670, 28096981, 32005694, 29655203, 16053902, 17958891, 31104665, 36403551, 33057194, 36406119, 35982159, 15121779)
ClinVar Genomic variation as it relates to human health
NM_014795.4(ZEB2):c.904C>T (p.Arg302Ter)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Pathogenic/Likely pathogenic
7 out of 9 submissions contributed to this classification
Help
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.
9
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_014795.4(ZEB2):c.904C>T (p.Arg302Ter)
Variation ID: 160329 Accession: VCV000160329.22
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q22.3 2: 144401211 (GRCh38) [ NCBI UCSC ] 2: 145158778 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Nov 23, 2014 Feb 25, 2025 Aug 7, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_014795.4:c.904C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055610.1:p.Arg302Ter nonsense NM_001171653.2:c.832C>T NP_001165124.1:p.Arg278Ter nonsense NC_000002.12:g.144401211G>A NC_000002.11:g.145158778G>A NG_016431.1:g.124181C>T - Protein change
- R302*, R278*
- Other names
-
p.R302*:CGA>TGA
NM_014795.4(ZEB2):c.904C>T
p.Arg302Ter
- Canonical SPDI
- NC_000002.12:144401210:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| ZEB2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1474 | 1550 | |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Jun 4, 2024 | RCV000148007.26 | |
| Pathogenic (2) |
criteria provided, single submitter
|
Aug 7, 2024 | RCV000167554.4 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Feb 08, 2013)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Mowat-Wilson syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000195505.1
First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 |
|
|
|
Pathogenic
(Aug 07, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000209418.12
First in ClinVar: Feb 24, 2015 Last updated: Sep 16, 2024 |
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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29093530, 25525159, 19842203, 24715670, 28096981, 32005694, 29655203, 16053902, 17958891, 31104665, 36403551, 33057194, 36406119, 35982159, 15121779) (less)
|
|
|
Pathogenic
(Jun 04, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Mowat-Wilson syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001414045.6
First in ClinVar: Jul 16, 2020 Last updated: Feb 25, 2025 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg302*) 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.Arg302*) 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: 15121779, 19842203). ClinVar contains an entry for this variant (Variation ID: 160329). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Nov 07, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Mowat-Wilson syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002045652.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
|
|
|
Pathogenic
(Jan 25, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: curation
|
Mowat-Wilson syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV003761408.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The heterozygous p.Arg302Ter variant in ZEB2 was identified by our study in one individual with periventricular heterotopia, agenesis of the corpus callosum, and seizures. Trio … (more)
The heterozygous p.Arg302Ter variant in ZEB2 was identified by our study in one individual with periventricular heterotopia, agenesis of the corpus callosum, and seizures. Trio exome analysis showed this variant to be de novo. The p.Arg302Ter variant in ZEB2 has been previously reported in at least 4 unrelated individuals with Mowat Wilson syndrome (PMID: 28096981, PMID: 29093530, PMID: 15121779, PMID: 19842203). The number of reported affected individuals with this variant is slightly greater than expected compared to non-affected individuals with this variant. This variant was found to be de novo in 2 individuals with confirmed paternity and maternity (PMID: 28096981, PMID: 29093530). This variant has also been reported in ClinVar (Variation ID: 160329) and has been interpreted as pathogenic by multiple submitters. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 302, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the ZEB2 gene is an established disease mechanism in autosomal dominant Mowat Wilson syndrome. In summary, this variant meets criteria to be classified as pathogenic for Mowat Wilson syndrome. ACMG/AMP Criteria applied: PVS1, PS2, PS4_Moderate, PM2_Supporting (Richards 2015). (less)
|
|
|
Pathogenic
(Apr 09, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Mowat-Wilson syndrome
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002020931.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
|
Likely pathogenic
(Apr 30, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Mowat-Wilson syndrome
Affected status: unknown
Allele origin:
germline
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV005652933.1
First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025 |
|
|
|
Pathogenic
(Jan 30, 2015)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000218433.1
First in ClinVar: Mar 28, 2015 Last updated: Mar 28, 2015 |
|
|
|
Pathogenic
(Mar 02, 2015)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: clinical testing
|
Mowat-Wilson syndrome
Affected status: yes
Allele origin:
unknown
|
Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics
Accession: SCV000221244.1
First in ClinVar: Apr 08, 2015 Last updated: Apr 08, 2015 |
|
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Arg302*) 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: 15121779, 19842203). ClinVar contains an entry for this variant (Variation ID: 160329). For these reasons, this variant has been classified as Pathogenic.
Comment:
The heterozygous p.Arg302Ter variant in ZEB2 was identified by our study in one individual with periventricular heterotopia, agenesis of the corpus callosum, and seizures. Trio exome analysis showed this variant to be de novo. The p.Arg302Ter variant in ZEB2 has been previously reported in at least 4 unrelated individuals with Mowat Wilson syndrome (PMID: 28096981, PMID: 29093530, PMID: 15121779, PMID: 19842203). The number of reported affected individuals with this variant is slightly greater than expected compared to non-affected individuals with this variant. This variant was found to be de novo in 2 individuals with confirmed paternity and maternity (PMID: 28096981, PMID: 29093530). This variant has also been reported in ClinVar (Variation ID: 160329) and has been interpreted as pathogenic by multiple submitters. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 302, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the ZEB2 gene is an established disease mechanism in autosomal dominant Mowat Wilson syndrome. In summary, this variant meets criteria to be classified as pathogenic for Mowat Wilson syndrome. ACMG/AMP Criteria applied: PVS1, PS2, PS4_Moderate, PM2_Supporting (Richards 2015).
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. |
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 observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29093530, 25525159, 19842203, 24715670, 28096981, 32005694, 29655203, 16053902, 17958891, 31104665, 36403551, 33057194, 36406119, 35982159, 15121779)
Comment:
This sequence change creates a premature translational stop signal (p.Arg302*) 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: 15121779, 19842203). ClinVar contains an entry for this variant (Variation ID: 160329). For these reasons, this variant has been classified as Pathogenic.
Comment:
The heterozygous p.Arg302Ter variant in ZEB2 was identified by our study in one individual with periventricular heterotopia, agenesis of the corpus callosum, and seizures. Trio exome analysis showed this variant to be de novo. The p.Arg302Ter variant in ZEB2 has been previously reported in at least 4 unrelated individuals with Mowat Wilson syndrome (PMID: 28096981, PMID: 29093530, PMID: 15121779, PMID: 19842203). The number of reported affected individuals with this variant is slightly greater than expected compared to non-affected individuals with this variant. This variant was found to be de novo in 2 individuals with confirmed paternity and maternity (PMID: 28096981, PMID: 29093530). This variant has also been reported in ClinVar (Variation ID: 160329) and has been interpreted as pathogenic by multiple submitters. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 302, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the ZEB2 gene is an established disease mechanism in autosomal dominant Mowat Wilson syndrome. In summary, this variant meets criteria to be classified as pathogenic for Mowat Wilson syndrome. ACMG/AMP Criteria applied: PVS1, PS2, PS4_Moderate, PM2_Supporting (Richards 2015).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| 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 |
Text-mined citations for rs587784571 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated May 17, 2025
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.