NM_025216.3(WNT10A):c.321C>A (p.Cys107Ter) AND WNT10A-related disorder

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 22, 2024
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:: RCV000779308.6

Allele description [Variation Report for NM_025216.3(WNT10A):c.321C>A (p.Cys107Ter)]

NM_025216.3(WNT10A):c.321C>A (p.Cys107Ter)

Gene:

WNT10A:Wnt family member 10A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_025216.3(WNT10A):c.321C>A (p.Cys107Ter)

HGVS:

NC_000002.12:g.218882368C>A
NG_012179.1:g.6836C>A
NM_025216.3:c.321C>AMANE SELECT
NP_079492.2:p.Cys107Ter
NC_000002.11:g.219747090C>A
NM_025216.2:c.321C>A

Protein change:

C107*; CYS107TER

Links:

OMIM: 606268.0002; dbSNP: rs121908119

NCBI 1000 Genomes Browser:

rs121908119

Molecular consequence:

NM_025216.3:c.321C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: WNT10A-related disorder
Synonyms:: WNT10A-Related Disorders; WNT10A-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

LRG_389t1 (0)
Nucleotide
PREDICTED: Mus musculus nuclear receptor subfamily 4, group A, member 1 (Nr4a1),...
PREDICTED: Mus musculus nuclear receptor subfamily 4, group A, member 1 (Nr4a1), transcript variant X5, mRNA
gi|1039748219|ref|XM_006520459.3|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000915891	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (Oct 31, 2018)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 22581971, 21834823, 19559398, 24902757, 23167694, 24449199, 24398796, 24702986 Citation Link,
SCV004116237	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 6, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005043953	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 22, 2024)	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

SCV000915891

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Pathogenic
(Oct 31, 2018)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link,

SCV004116237

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 6, 2024)

germline

clinical testing

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

SCV005043953

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 22, 2024)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in WNT10A are present in more than half of isolated hypodontia cases.

van den Boogaard MJ, Créton M, Bronkhorst Y, van der Hout A, Hennekam E, Lindhout D, Cune M, Ploos van Amstel HK.

J Med Genet. 2012 May;49(5):327-31. doi: 10.1136/jmedgenet-2012-100750.

PubMed [citation]

PMID:: 22581971

Schöpf-Schulz-Passarge syndrome resulting from a homozygous nonsense mutation, p.Cys107X, in WNT10A.

Petrof G, Fong K, Lai-Cheong JE, Cockayne SE, McGrath JA.

Australas J Dermatol. 2011 Aug;52(3):224-6. doi: 10.1111/j.1440-0960.2011.00788.x. Epub 2011 Jun 29.

PubMed [citation]

PMID:: 21834823

See all PubMed Citations (9)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000915891.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

The WNT10A c.321C>A (p.Cys107Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. Across a selection of the available literature involving probands with WNT10A-related disorders consisting of a spectrum of phenotypes including odontoonychodermal dysplasia, Schopf-Schulz-Passarge syndrome and selective tooth agenesis, the variant was found in a homozygous state in 12 individuals, in a compound heterozygous state in a total of 30 individuals, and in 29 symptomatic heterozygous individuals (Bohring et al. 2009; Petrof et al. 2011; Van den Boogaard et al. 2012; Mostowska et al. 2013; Clauss et al. 2014; Tziotzios et al. 2014; Vink et al. 2014; Arzoo et al. 2014). The variant was absent from 800 control subjects but is reported at a frequency of 0.00140 in the European American population of the Exome Sequencing Project. Due to the potential impact of stop-gained variants and available evidence, the p.Cys107Ter variant is classified as pathogenic for WNT10A-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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 PreventionGenetics, part of Exact Sciences, SCV004116237.2

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

Description

The WNT10A c.321C>A variant is predicted to result in premature protein termination (p.Cys107*). This variant has been reported in the compound heterozygous and homozygous states to be pathogenic for ectodermal dysplasia (Bohring et al. 2009. PubMed ID: 19559398; Vink et al. 2014. PubMed ID: 24398796; Guazzarotti et al. 2018. PubMed ID: 28976000). This variant has also been reported in the heterozygous state to be pathogenic for abnormal tooth shape and tooth number (Vink et al. 2014. PubMed ID: 24398796). This variant is reported in 0.13% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in WNT10A are expected to be pathogenic. This variant is interpreted as pathogenic.

#	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 Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV005043953.1

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

Description

PVS1, PS3_Supporting, PM1, PM3_Very Strong, PP1

#	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: Aug 18, 2024

ClinVar

Relating variation to medicine