ClinVar Genomic variation as it relates to human health
NM_025216.3(WNT10A):c.321C>A (p.Cys107Ter)
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
-
NM_025216.3(WNT10A):c.321C>A (p.Cys107Ter)
Variation ID: 4461 Accession: VCV000004461.49
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q35 2: 218882368 (GRCh38) [ NCBI UCSC ] 2: 219747090 (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 Mar 10, 2017 May 19, 2024 Mar 22, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_025216.3:c.321C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_079492.2:p.Cys107Ter nonsense NC_000002.12:g.218882368C>A NC_000002.11:g.219747090C>A NG_012179.1:g.6836C>A - Protein change
- C107*
- Other names
- -
- Canonical SPDI
- NC_000002.12:218882367:C: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.
Exome Aggregation Consortium (ExAC) 0.00059
The Genome Aggregation Database (gnomAD), exomes 0.00062
Trans-Omics for Precision Medicine (TOPMed) 0.00084
The Genome Aggregation Database (gnomAD) 0.00087
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. |
|||
WNT10A | - | - |
GRCh38 GRCh37 |
501 | 554 |
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 (2) |
criteria provided, single submitter
|
Mar 12, 2024 | RCV000004715.7 | |
Pathogenic (2) |
no assertion criteria provided
|
Sep 16, 2020 | RCV000004716.5 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Jan 2, 2024 | RCV000030650.14 | |
Pathogenic (1) |
criteria provided, single submitter
|
Sep 7, 2014 | RCV000190800.4 | |
Pathogenic (11) |
criteria provided, multiple submitters, no conflicts
|
Jan 1, 2024 | RCV000255732.24 | |
Pathogenic (3) |
criteria provided, single submitter
|
Oct 31, 2018 | RCV000477935.5 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 31, 2024 | RCV000536747.9 | |
WNT10A-related disorder
|
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 22, 2024 | RCV000779308.6 |
not provided (1) |
no classification provided
|
- | RCV001729335.2 | |
Pathogenic (1) |
criteria provided, single submitter
|
Mar 30, 2023 | RCV002247247.2 |
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
(Aug 17, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000331436.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
|
|
Pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
WNT10A-Related Disorders
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000915891.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
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 … (more)
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. (less)
|
|
Pathogenic
(Jan 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Tooth agenesis, selective, 4
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002061215.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
The c.321C>A;p.(Cys107*) variant creates a premature translational stop signal in the WNT10A gene. It is expected to result in an absent or disrupted protein product … (more)
The c.321C>A;p.(Cys107*) variant creates a premature translational stop signal in the WNT10A gene. It is expected to result in an absent or disrupted protein product -PVS1.This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 4461; PMID: 28105635; 26964878; 25629078; 25545742; 24902757; 24449199; 19559398; 21279306) - PS4. The p.(Cys107*) was detected in trans with a pathogenic variant (PMID: 28105635; PMID: 26964878; 25629078; 24902757; 19559398; 21279306) - PM3_strong. The variant co-segregated with disease in multiple affected family members (PMID: 26964878; 25629078; 19559398; 21279306) - PP1_strong and is allele frequency is greater than expected for disorder - BS1. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Uruguay
|
|
Pathogenic
(Dec 07, 2021)
|
criteria provided, single submitter
Method: research
|
Tooth agenesis, selective, 4
Affected status: unknown
Allele origin:
unknown
|
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill
Study: CSER_NCGENES_2
Accession: SCV002587033.1 First in ClinVar: Oct 29, 2022 Last updated: Oct 29, 2022
Comment:
WNT10A c.321C>A p.(Cys107Ter) is a nonsense variant which is predicted to introduce a premature termination codon in exon 2 (out of 4 total exons). Loss … (more)
WNT10A c.321C>A p.(Cys107Ter) is a nonsense variant which is predicted to introduce a premature termination codon in exon 2 (out of 4 total exons). Loss of normal protein function is predicted, either through nonsense-mediated mRNA decay or protein truncation. This variant is one of the most commonly observed pathogenic WNT10A variants (PMID 20301291) and has been identified in the heterozygous state in individuals with no clinical phenotype, isolated tooth agenesis/hypodontia, or relatively mild ectodermal dysplasia (PMID 19559398, 21834823, 22581971, 24398796, 25629078). WNT10A c.321C>A p.(Cys107Ter) has been observed in the homozygous or compound heterozygous state in individuals with isolated oligodontia or ectodermal dysplasia (PMID 19559398, 21834823, 22581971, 24398796, 25629078). This variant has also been observed to segregate with disease in mutiple families (PMID 19559398, 24398796, 25629078), therefore is classified as pathogenic. (less)
|
Number of individuals with the variant: 1
Clinical Features:
Maxillary lateral incisor microdontia (present) , Increased susceptibility to fractures (present) , Recurrent fractures (present) , Fractures of the long bones (present) , Fractured ulna … (more)
Maxillary lateral incisor microdontia (present) , Increased susceptibility to fractures (present) , Recurrent fractures (present) , Fractures of the long bones (present) , Fractured ulna (present) , Bowing of limbs due to multiple fractures (absent) , Multiple prenatal fractures (absent) (less)
|
|
Pathogenic
(Sep 07, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary disease
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000244241.6
First in ClinVar: Sep 14, 2015 Last updated: Dec 11, 2022 |
Comment:
Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Clinical Features:
MR/ID/DD (present) , Brain MRI positive (present) , Dysmorphic features (present) , FTT/Undergrowth (present) , Hypotonia (present) , Audiologic/Otolaryngologic (child onset) (present) , Craniofacial (child … (more)
MR/ID/DD (present) , Brain MRI positive (present) , Dysmorphic features (present) , FTT/Undergrowth (present) , Hypotonia (present) , Audiologic/Otolaryngologic (child onset) (present) , Craniofacial (child onset) (present) , Dental (child onset) (present) , Dermatologic (child onset) (present) , Gastrointestinal (child onset) (present) , Metabolic/ Biochemical (child onset) (present) , Musculoskeletal/Structural (child onset) (present) , Neurologic (child onset) (present) (less)
Family history: yes
Sex: female
Segregation observed: yes
|
|
Pathogenic
(Oct 26, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002020911.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Mar 12, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Odonto-onycho-dermal dysplasia
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005039405.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Comment:
Variant summary: WNT10A c.321C>A (p.Cys107X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: WNT10A c.321C>A (p.Cys107X) 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. The variant allele was found at a frequency of 0.00062 in 251318 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in WNT10A causing Odonto-onycho-dermal dysplasia (0.00062 vs ND), allowing no conclusion about variant significance. c.321C>A has been reported in the literature in multiple individuals affected with Odonto-onycho-dermal dysplasia. 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. ClinVar contains an entry for this variant (Variation ID: 4461). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
Pathogenic
(Jan 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004699501.3
First in ClinVar: Mar 10, 2024 Last updated: May 12, 2024 |
Comment:
WNT10A: PM3:Very Strong, PVS1, PP1:Strong, PM2
Number of individuals with the variant: 1
|
|
Pathogenic
(Jan 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Tooth agenesis, selective, 4
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV005043902.1
First in ClinVar: May 19, 2024 Last updated: May 19, 2024 |
Comment:
PVS1, PM3_Strong
|
|
Pathogenic
(Mar 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
WNT10A-related disorder
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV005043953.1
First in ClinVar: May 19, 2024 Last updated: May 19, 2024 |
Comment:
PVS1, PS3_Supporting, PM1, PM3_Very Strong, PP1
|
|
Pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Tooth agenesis, selective, 4
SchC6pf-Schulz-Passarge syndrome Odonto-onycho-dermal dysplasia
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000893580.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
Pathogenic
(Sep 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000322007.7
First in ClinVar: Oct 09, 2016 Last updated: Apr 17, 2019 |
Comment:
One of the most common pathogenic variants reported in the WNT10A gene (Vink et al., 2014) Observed in the homozygous state or in trans with … (more)
One of the most common pathogenic variants reported in the WNT10A gene (Vink et al., 2014) Observed in the homozygous state or in trans with a second pathogenic variant in individuals with either isolated oligodontia or other features of ectodermal dysplasia (Bohring et al., 2009; Cluzeau et al., 2011; Plaisancie et al., 2013; Mostowska et al., 2013; Clauss et al., 2014; Tardieu et al., 2017) Identified in the heterozygous state in individuals with isolated hypodontia or oligodontia, individuals with features of ectodermal dysplasia, and unaffected carriers (Bohring et al., 2009; Cluzeau et al., 2011; van den Boogaard et al., 2012; Mostowska et al., 2013) 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 Observed in 0.064% (181/282692 alleles) in large population cohorts (Lek et al., 2016) (less)
|
|
Pathogenic
(Sep 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Tooth agenesis, selective, 4
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002580319.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS4, PM3, PP1_MOD, PM2_SUP
|
Number of individuals with the variant: 1
Sex: male
|
|
Pathogenic
(Mar 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Mendelics
Accession: SCV002516173.2
First in ClinVar: May 28, 2022 Last updated: Apr 01, 2023 |
|
|
Pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010940.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Tooth agenesis, selective, 4
Odonto-onycho-dermal dysplasia
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000638465.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Cys107*) in the WNT10A gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Cys107*) in the WNT10A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WNT10A are known to be pathogenic (PMID: 17847007, 22581971, 25629078). This variant is present in population databases (rs121908119, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with odonto-onycho-dermal dysplasia, Schopf-Schultz-Passarge syndrome, and isolated tooth agenesis (PMID: 19559398, 23167694, 24398796, 25545742, 25629078). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4461). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Feb 06, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
WNT10A-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004116237.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
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 … (more)
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. (less)
|
|
Pathogenic
(May 01, 2012)
|
no assertion criteria provided
Method: literature only
|
ODONTOONYCHODERMAL DYSPLASIA
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000024890.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2017 |
Comment on evidence:
In affected members of 3 families with odontoonychodermal dysplasia (OODD; 257980) and 1 proband of a family with Schopf-Schulz-Passarge syndrome (SPSS; 224750), Bohring et al. … (more)
In affected members of 3 families with odontoonychodermal dysplasia (OODD; 257980) and 1 proband of a family with Schopf-Schulz-Passarge syndrome (SPSS; 224750), Bohring et al. (2009) identified homozygosity for a 321C-A transversion in the WNT10A gene, resulting in a cys107-to-ter (C107X) substitution that was not found in 200 control chromosomes. In 2 additional probands with OODD, the C107X mutation was found in compound heterozygosity with a phe228-to-ile (F228I; 606268.0003) mutation, and in a brother and sister who had oligodontia and sparse body hair and eyebrows as their only manifestations, the C107X mutation was found in compound heterozygosity with an arg128-to-gln (R128Q; 606268.0004) mutation. Of 18 heterozygous carriers of the C107X mutation, 10 exhibited some phenotypic manifestation, including anomalies of teeth, skin, and nails. In 2 unrelated patients with nonsyndromic tooth agenesis (STHAG4; 150400), van den Boogaard et al. (2012) identified heterozygosity for the C107X mutation in the WNT10A gene; in 3 other patients, the mutation was present in compound heterozygosity with the F228I mutation. In addition, van den Boogaard et al. (2012) identified mutations in the C107X mutation in 6 patients with tooth agenesis who had mild features of ectodermal dysplasia, but who did not exhibit the characteristic features of OODD; 2 were heterozygous, 1 was homozygous, and 3 were compound heterozygous for C207X and F228I. In 4 probands with tooth agenesis and features of ectodermal dysplasia, Plaisancie et al. (2013) identified the C107X mutation in the WNT10A gene, present in homozygosity in 1 patient and in compound heterozygosity in 3 patients, including with the F228I mutation in 1 proband. In the latter family, the proband's unaffected father and mother were each heterozygous for 1 of the mutations. (less)
|
|
Pathogenic
(May 01, 2012)
|
no assertion criteria provided
Method: literature only
|
SCHOPF-SCHULZ-PASSARGE SYNDROME
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000024891.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2017 |
Comment on evidence:
In affected members of 3 families with odontoonychodermal dysplasia (OODD; 257980) and 1 proband of a family with Schopf-Schulz-Passarge syndrome (SPSS; 224750), Bohring et al. … (more)
In affected members of 3 families with odontoonychodermal dysplasia (OODD; 257980) and 1 proband of a family with Schopf-Schulz-Passarge syndrome (SPSS; 224750), Bohring et al. (2009) identified homozygosity for a 321C-A transversion in the WNT10A gene, resulting in a cys107-to-ter (C107X) substitution that was not found in 200 control chromosomes. In 2 additional probands with OODD, the C107X mutation was found in compound heterozygosity with a phe228-to-ile (F228I; 606268.0003) mutation, and in a brother and sister who had oligodontia and sparse body hair and eyebrows as their only manifestations, the C107X mutation was found in compound heterozygosity with an arg128-to-gln (R128Q; 606268.0004) mutation. Of 18 heterozygous carriers of the C107X mutation, 10 exhibited some phenotypic manifestation, including anomalies of teeth, skin, and nails. In 2 unrelated patients with nonsyndromic tooth agenesis (STHAG4; 150400), van den Boogaard et al. (2012) identified heterozygosity for the C107X mutation in the WNT10A gene; in 3 other patients, the mutation was present in compound heterozygosity with the F228I mutation. In addition, van den Boogaard et al. (2012) identified mutations in the C107X mutation in 6 patients with tooth agenesis who had mild features of ectodermal dysplasia, but who did not exhibit the characteristic features of OODD; 2 were heterozygous, 1 was homozygous, and 3 were compound heterozygous for C207X and F228I. In 4 probands with tooth agenesis and features of ectodermal dysplasia, Plaisancie et al. (2013) identified the C107X mutation in the WNT10A gene, present in homozygosity in 1 patient and in compound heterozygosity in 3 patients, including with the F228I mutation in 1 proband. In the latter family, the proband's unaffected father and mother were each heterozygous for 1 of the mutations. (less)
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809658.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001975496.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
Pathogenic
(May 01, 2012)
|
no assertion criteria provided
Method: literature only
|
TOOTH AGENESIS, SELECTIVE 4
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000053328.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 10, 2017 |
Comment on evidence:
In affected members of 3 families with odontoonychodermal dysplasia (OODD; 257980) and 1 proband of a family with Schopf-Schulz-Passarge syndrome (SPSS; 224750), Bohring et al. … (more)
In affected members of 3 families with odontoonychodermal dysplasia (OODD; 257980) and 1 proband of a family with Schopf-Schulz-Passarge syndrome (SPSS; 224750), Bohring et al. (2009) identified homozygosity for a 321C-A transversion in the WNT10A gene, resulting in a cys107-to-ter (C107X) substitution that was not found in 200 control chromosomes. In 2 additional probands with OODD, the C107X mutation was found in compound heterozygosity with a phe228-to-ile (F228I; 606268.0003) mutation, and in a brother and sister who had oligodontia and sparse body hair and eyebrows as their only manifestations, the C107X mutation was found in compound heterozygosity with an arg128-to-gln (R128Q; 606268.0004) mutation. Of 18 heterozygous carriers of the C107X mutation, 10 exhibited some phenotypic manifestation, including anomalies of teeth, skin, and nails. In 2 unrelated patients with nonsyndromic tooth agenesis (STHAG4; 150400), van den Boogaard et al. (2012) identified heterozygosity for the C107X mutation in the WNT10A gene; in 3 other patients, the mutation was present in compound heterozygosity with the F228I mutation. In addition, van den Boogaard et al. (2012) identified mutations in the C107X mutation in 6 patients with tooth agenesis who had mild features of ectodermal dysplasia, but who did not exhibit the characteristic features of OODD; 2 were heterozygous, 1 was homozygous, and 3 were compound heterozygous for C207X and F228I. In 4 probands with tooth agenesis and features of ectodermal dysplasia, Plaisancie et al. (2013) identified the C107X mutation in the WNT10A gene, present in homozygosity in 1 patient and in compound heterozygosity in 3 patients, including with the F228I mutation in 1 proband. In the latter family, the proband's unaffected father and mother were each heterozygous for 1 of the mutations. (less)
|
|
Pathogenic
(Aug 13, 2016)
|
no assertion criteria provided
Method: research
|
Tooth agenesis, selective, 4
Odonto-onycho-dermal dysplasia SchC6pf-Schulz-Passarge syndrome
Affected status: unknown
Allele origin:
germline
|
Division of Human Genetics, Children's Hospital of Philadelphia
Study: CSER-PediSeq
Accession: SCV000536908.1 First in ClinVar: Apr 23, 2017 Last updated: Apr 23, 2017 |
|
|
Pathogenic
(Jun 25, 2018)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
de novo
|
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals
Accession: SCV000898154.1
First in ClinVar: Apr 19, 2019 Last updated: Apr 19, 2019 |
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Schopf-Schulz-Passarge syndrome
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001459907.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743586.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931148.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001956755.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Pathogenic
(Aug 04, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Tooth agenesis, selective, 4
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein
Accession: SCV002011765.1
First in ClinVar: Nov 06, 2021 Last updated: Nov 06, 2021 |
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Odonto-onycho-dermal dysplasia
SchC6pf-Schulz-Passarge syndrome Tooth agenesis, selective, 4
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749714.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
Variant interpreted as Pathogenic and reported on 10-03-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report … (more)
Variant interpreted as Pathogenic and reported on 10-03-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormal oral cavity morphology (present) , Hyperpigmentation of the skin (present) , Thickened skin (present) , Asthma (present) , Recurrent infections (present) , Abnormal intestine … (more)
Abnormal oral cavity morphology (present) , Hyperpigmentation of the skin (present) , Thickened skin (present) , Asthma (present) , Recurrent infections (present) , Abnormal intestine morphology (present) , Abnormal stomach morphology (present) , Anxiety (present) , Abnormal delivery (present) (less)
Indication for testing: Diagnostic, Family Testing
Age: 30-39 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2019-10-03
Testing laboratory interpretation: Pathogenic
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Ectodermal dysplasia
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV001977602.2
First in ClinVar: Oct 16, 2021 Last updated: Oct 01, 2022 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
Dental and extra-oral clinical features in 41 patients with WNT10A gene mutations: A multicentric genotype-phenotype study. | Tardieu C | Clinical genetics | 2017 | PMID: 28105635 |
Odonto-onycho-dermal dysplasia in a patient homozygous for a WNT10A nonsense mutation and mild manifestations of ectodermal dysplasia in carriers of the mutation. | Krøigård AB | BMC dermatology | 2016 | PMID: 26964878 |
Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds. | Yang J | Molecular genetics & genomic medicine | 2015 | PMID: 25629078 |
WNT10A coding variants and maxillary lateral incisor agenesis with associated dental anomalies. | Mostowska A | European journal of oral sciences | 2015 | PMID: 25545742 |
Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. | Farwell KD | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25356970 |
Clinical features and WNT10A mutations in seven unrelated cases of Schöpf-Schulz-Passarge syndrome. | Tziotzios C | The British journal of dermatology | 2014 | PMID: 24902757 |
Dento-maxillo-facial phenotype and implants-based oral rehabilitation in Ectodermal Dysplasia with WNT10A gene mutation: report of a case and literature review. | Clauss F | Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery | 2014 | PMID: 24702986 |
The WNT10A gene in ectodermal dysplasias and selective tooth agenesis. | Mues G | American journal of medical genetics. Part A | 2014 | PMID: 24700731 |
WNT10A mutations account for ¼ of population-based isolated oligodontia and show phenotypic correlations. | Arzoo PS | American journal of medical genetics. Part A | 2014 | PMID: 24449199 |
Variability in dentofacial phenotypes in four families with WNT10A mutations. | Vink CP | European journal of human genetics : EJHG | 2014 | PMID: 24398796 |
WNT10A variants are associated with non-syndromic tooth agenesis in the general population. | Song S | Human genetics | 2014 | PMID: 24043634 |
Mutations in WNT10A are frequently involved in oligodontia associated with minor signs of ectodermal dysplasia. | Plaisancié J | American journal of medical genetics. Part A | 2013 | PMID: 23401279 |
Nucleotide variants of genes encoding components of the Wnt signalling pathway and the risk of non-syndromic tooth agenesis. | Mostowska A | Clinical genetics | 2013 | PMID: 23167694 |
Mutations in WNT10A are present in more than half of isolated hypodontia cases. | van den Boogaard MJ | Journal of medical genetics | 2012 | PMID: 22581971 |
Schöpf-Schulz-Passarge syndrome resulting from a homozygous nonsense mutation, p.Cys107X, in WNT10A. | Petrof G | The Australasian journal of dermatology | 2011 | PMID: 21834823 |
Intra-familial variability of ectodermal defects associated with WNT10A mutations. | Wedgeworth EK | Acta dermato-venereologica | 2011 | PMID: 21279306 |
WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. | Bohring A | American journal of human genetics | 2009 | PMID: 19559398 |
Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. | Adaimy L | American journal of human genetics | 2007 | PMID: 17847007 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=WNT10A | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs121908119 ...
HelpRecord last updated Jun 02, 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.