NM_014795.4(ZEB2):c.1381C>T (p.Gln461Ter) AND Mowat-Wilson syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 7, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001387154.17

Allele description [Variation Report for NM_014795.4(ZEB2):c.1381C>T (p.Gln461Ter)]

NM_014795.4(ZEB2):c.1381C>T (p.Gln461Ter)

Gene:

ZEB2:zinc finger E-box binding homeobox 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q22.3

Genomic location:

Preferred name:

NM_014795.4(ZEB2):c.1381C>T (p.Gln461Ter)

HGVS:

NC_000002.12:g.144399806G>A
NG_016431.1:g.125586C>T
NM_001171653.2:c.1309C>T
NM_014795.4:c.1381C>TMANE SELECT
NP_001165124.1:p.Gln437Ter
NP_055610.1:p.Gln461Ter
NC_000002.11:g.145157373G>A
NM_014795.3:c.1381C>T
NP_055610.1:p.Gln461*
NP_055610.1:p.Gln461*

Protein change:

Q437*

Links:

dbSNP: rs398124274

NCBI 1000 Genomes Browser:

rs398124274

Molecular consequence:

NM_001171653.2:c.1309C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_014795.4:c.1381C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Mowat-Wilson syndrome (MOWS)
Synonyms:: Mental retardation, microcephaly, and distinct facial features with or without Hirschsprung disease; Hirschsprung disease mental retardation syndrome
Identifiers:: MONDO: MONDO:0009341; MedGen: C1856113; Orphanet: 2152; OMIM: 235730

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001587706	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 23, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16053902, 12784289, 24092421, 28492532
SCV002045649	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	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

SCV001587706

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 23, 2020)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002045649

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 7, 2021)

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
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and mutational spectrum of Mowat-Wilson syndrome.

Zweier C, Thiel CT, Dufke A, Crow YJ, Meinecke P, Suri M, Ala-Mello S, Beemer F, Bernasconi S, Bianchi P, Bier A, Devriendt K, Dimitrov B, Firth H, Gallagher RC, Garavelli L, Gillessen-Kaesbach G, Hudgins L, Kääriäinen H, Karstens S, Krantz I, Mannhardt A, et al.

Eur J Med Genet. 2005 Apr-Jun;48(2):97-111. Epub 2005 Feb 25.

PubMed [citation]

PMID:: 16053902

Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B.

Wilson M, Mowat D, Dastot-Le Moal F, Cacheux V, Kääriäinen H, Cass D, Donnai D, Clayton-Smith J, Townshend S, Curry C, Gattas M, Braddock S, Kerr B, Aftimos S, Zehnwirth H, Barrey C, Goossens M.

Am J Med Genet A. 2003 Jun 15;119A(3):257-65.

PubMed [citation]

PMID:: 12784289

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001587706.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ZEB2 are known to be pathogenic (PMID: 16053902). This variant has been observed in individual(s) with clinical features of Mowat-Wilson syndrome (PMID: 12784289, 24092421). ClinVar contains an entry for this variant (Variation ID: 95620). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln461*) in the ZEB2 gene. It is expected to result in an absent or disrupted protein product.

#	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

From Genome-Nilou Lab, SCV002045649.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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