ClinVar Miner

Submissions for variant NM_025216.3(WNT10A):c.682T>A (p.Phe228Ile) (rs121908120)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255788 SCV000322010 pathogenic not provided 2019-01-09 criteria provided, single submitter clinical testing The F228I variant in the WNT10A gene is one of the most common pathogenic variants reported in this gene, either in the homozygous state or in trans with a second pathogenic variant, in individuals with either isolated oligodontia or with 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). The F228I variant has also been reported in the heterozygous state in many individuals with isolated hypodontia or oligodontia, in individuals with features of ectodermal dysplasia, and in unaffected carriers (Bohring et al., 2009; Kantaputra et al., 2011; Cluzeau et al., 2011; van den Boogaard et al., 2012; Mostowska et al., 2013; Plaisancie et al., 2013; Tardieu et al., 2017). While the F228I variant is a conservative amino acid substitution, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret F228I as a pathogenic variant.
Illumina Clinical Services Laboratory,Illumina RCV000445356 SCV000427565 likely benign Tooth agenesis, selective, 4 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000278695 SCV000427566 likely benign Schopf-Schulz-Passarge syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000004717 SCV000427567 likely benign Odonto-onycho-dermal dysplasia 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455454 SCV000540673 likely benign not specified 2016-03-29 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 241/13000=1.85%
Invitae RCV000550721 SCV000638469 benign Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000622932 SCV000741335 pathogenic Inborn genetic diseases 2015-12-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
Breda Genetics srl RCV000754840 SCV000882567 pathogenic Hypohidrotic ectodermal dysplasia 2016-08-29 criteria provided, single submitter clinical testing This variant has been identified in an individual with congenital alopecia, hypodontia, and hypohidrosis. In the family, inheritance was compatible with a dominant pattern. This nonsynonymous variant is reported with an estimated allele frequency of 0.014 in gnomAD exomes, 0.01215 in gnomAD genomes, and 0.019 in NHLI Exome Sequencing Project (ESP). The nucleotide position is conserved across 35 mammalian species (GERP RS: 4.46). In silico analysis indicates that the variant might be damaging (MutationTaster: disease-causing; FATHMM-MKL: damaging; Provean: damaging; DANN: 0.992). The p.Phe228Ile mutation represents the most common allele identified in cases with isolated hypodontia (PMIDs: 22581971, 24449199, 24700731). Reduced penetrance and variable expressivity have been reported in carriers of the p.Phe228Ile mutation. Nearly half of heterozygotes may display mild multifocal symptoms, such as variable abnormalities of skin, hair, teeth or nails (PMIDs: 19559398, 21279306). For instance, van den Boogaard et al. (PMID: 22581971) reported a p.Phe228Ile heterozygote presenting with hypodontia, alopecia, hypohidrosis and mild nail dysplasia. Autosomal dominant inheritance of isolated hypodontia-microdontia in p.Phe228Ile heterozygotes has been described also by Kantaputra and Sripathomsawat (PMID: 21484994).
Mendelics RCV000004717 SCV001136221 uncertain significance Odonto-onycho-dermal dysplasia 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000255788 SCV001248938 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing
OMIM RCV000004717 SCV000024892 pathogenic Odonto-onycho-dermal dysplasia 2014-02-01 no assertion criteria provided literature only
OMIM RCV000445356 SCV000536682 pathogenic Tooth agenesis, selective, 4 2014-02-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics,Yale University RCV000845113 SCV000987049 pathogenic Reduced number of teeth 2014-09-15 no assertion criteria provided literature only

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