Submissions for variant NM_025216.3(WNT10A):c.383G>A (p.Arg128Gln)

gnomAD frequency: 0.00007  dbSNP: rs121908121

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000824631	SCV000965536	pathogenic	Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 128 of the WNT10A protein (p.Arg128Gln). This variant is present in population databases (rs121908121, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal dominant oligodontia and clinical features of ectodermal dysplasia (PMID: 19559398, 22581971; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4463). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on WNT10A protein function. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000004718	SCV001367525	likely pathogenic	Odonto-onycho-dermal dysplasia	2019-02-20	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PP3,PS1.
GeneDx	RCV000059803	SCV002762100	likely pathogenic	not provided	2022-08-23	criteria provided, single submitter	clinical testing	Observed in the heterozygous state in a patient with isolated oligodontia in published literature (Ross et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 19559398, 34228861, 22581971)
OMIM	RCV000004718	SCV000024893	pathogenic	Odonto-onycho-dermal dysplasia	2012-05-01	no assertion criteria provided	literature only
OMIM	RCV000030651	SCV000053329	pathogenic	Tooth agenesis, selective, 4	2012-05-01	no assertion criteria provided	literature only
UniProtKB/Swiss-Prot	RCV000059803	SCV000091373	not provided	not provided		no assertion provided	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000059803	SCV001740230	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000059803	SCV001927530	pathogenic	not provided		no assertion criteria provided	clinical testing