NM_014795.4(ZEB2):c.3535A>G (p.Ile1179Val) AND Mowat-Wilson syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jul 12, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV002181513.8

Allele description [Variation Report for NM_014795.4(ZEB2):c.3535A>G (p.Ile1179Val)]

NM_014795.4(ZEB2):c.3535A>G (p.Ile1179Val)

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.3535A>G (p.Ile1179Val)

HGVS:

NC_000002.12:g.144389561T>C
NG_016431.1:g.135831A>G
NM_001171653.2:c.3463A>G
NM_014795.3:c.3535A>G
NM_014795.4:c.3535A>GMANE SELECT
NP_001165124.1:p.Ile1155Val
NP_055610.1:p.Ile1179Val
NC_000002.11:g.145147128T>C

Protein change:

I1155V

Links:

dbSNP: rs1360979536

NCBI 1000 Genomes Browser:

rs1360979536

Molecular consequence:

NM_001171653.2:c.3463A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014795.4:c.3535A>G - missense variant - [Sequence Ontology: SO:0001583]

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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Arcocellulus cornucervis isolate RCC2270 internal transcribed spacer 2, partial ...
Arcocellulus cornucervis isolate RCC2270 internal transcribed spacer 2, partial sequence
gi|1371545958|gb|MH129016.1|

Nucleotide
1545364[uid] (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002486693	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jul 12, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004100651	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV002486693

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jul 12, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004100651

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

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, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Invitae, SCV002486693.3

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004100651.1

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

Description

The missense variant p.I1179V in ZEB2 (NM_014795.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The missense variant c.3535A>G (p.I1179V) in ZEB2 (NM_014795.4) is observed in 1/30616 (0.0033%) alleles from individuals of South Asian background in the gnomAD dataset (Exome Aggregation Consortium et al., 2016), but was not seen in the homozygous state. For these reasons, this variant has been classified as Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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