Submissions for variant NM_025216.3(WNT10A):c.694del (p.Arg232fs)

dbSNP: rs1575233692

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000792132	SCV000931410	pathogenic	Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4	2023-08-16	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 639357). This sequence change creates a premature translational stop signal (p.Arg232Glyfs*11) in the WNT10A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 186 amino acid(s) of the WNT10A protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WNT10A-related conditions. This variant disrupts a region of the WNT10A protein in which other variant(s) (p.Arg248*) have been determined to be pathogenic (PMID: 20979233, 28981473; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV001784406	SCV002017947	likely pathogenic	not provided	2021-02-02	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV002290429	SCV002581090	likely pathogenic	Odonto-onycho-dermal dysplasia	2022-07-26	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002507361	SCV002815093	likely pathogenic	Odonto-onycho-dermal dysplasia; SchC6pf-Schulz-Passarge syndrome; Tooth agenesis, selective, 4	2021-09-29	criteria provided, single submitter	clinical testing
Molecular Genetics, Royal Melbourne Hospital	RCV002290429	SCV004812429	likely pathogenic	Odonto-onycho-dermal dysplasia	2022-10-06	criteria provided, single submitter	clinical testing	This sequence change in WNT10A is a frameshift variant that may cause a premature stop codon, p.(Arg232Glyfs*11), that is predicted to escape nonsense-mediated decay, however, it is a truncation of a functionally important region (removes amino acids 242-252) in a gene where loss of function is an established disease mechanism (PMID: 25629078, 29178643). This variant is absent from the population database gnomAD v2.1 and v3.1. To our knowledge, this variant has not been reported in the literature in any individuals with WNT10A-related disease. This variant has been classified as likely pathogenic and pathogenic in ClinVar (Variation ID: 639357). This variant has been detected homozygous in at least one individual with a phenotype consistent with odontoonychodermal dysplasia (Royal Melbourne Hospital). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PVS1_Strong, PM2_Supporting, PM3_Supporting.