2-218882357-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_025216.3(WNT10A):c.310C>T(p.Arg104Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R104H) has been classified as Likely pathogenic.
Frequency
Consequence
NM_025216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNT10A | NM_025216.3 | c.310C>T | p.Arg104Cys | missense_variant | 2/4 | ENST00000258411.8 | |
WNT10A | XM_011511929.3 | c.214C>T | p.Arg72Cys | missense_variant | 3/5 | ||
WNT10A | XM_011511930.2 | c.310C>T | p.Arg104Cys | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNT10A | ENST00000258411.8 | c.310C>T | p.Arg104Cys | missense_variant | 2/4 | 1 | NM_025216.3 | P1 | |
WNT10A | ENST00000458582.1 | c.199C>T | p.Arg67Cys | missense_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251376Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135878
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727244
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 104 of the WNT10A protein (p.Arg104Cys). This variant is present in population databases (rs764658964, gnomAD 0.07%). This missense change has been observed in individual(s) with ectodermal dysplasia and tooth agenesis (PMID: 29271000, 30974434; 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: 532827). 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) performed at Invitae indicates that this missense variant is expected to disrupt WNT10A protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. - |
Odonto-onycho-dermal dysplasia Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Department of Second Dental Center, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 31, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25629078, 30426266, 29271000, 30974434) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at