chr2-218892848-G-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PS1PM2PP3_Strong
The NM_025216.3(WNT10A):c.831G>T(p.Trp277Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,589,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar.
Frequency
Consequence
NM_025216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNT10A | NM_025216.3 | c.831G>T | p.Trp277Cys | missense_variant | 4/4 | ENST00000258411.8 | |
WNT10A | XM_011511929.3 | c.735G>T | p.Trp245Cys | missense_variant | 5/5 | ||
WNT10A | XM_011511930.2 | c.451G>T | p.Ala151Ser | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNT10A | ENST00000258411.8 | c.831G>T | p.Trp277Cys | missense_variant | 4/4 | 1 | NM_025216.3 | P1 | |
WNT10A | ENST00000458582.1 | c.340G>T | p.Ala114Ser | missense_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000139 AC: 2AN: 1437542Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 2AN XY: 712948
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74370
ClinVar
Submissions by phenotype
SchC6pf-Schulz-Passarge syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 13, 2020 | - - |
Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 14, 2023 | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with both dominant and recessive WNT10A-related disease (PMID: 22581971, 24700731, 26087098, 28976000; Invitae). ClinVar contains an entry for this variant (Variation ID: 532830). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 277 of the WNT10A protein (p.Trp277Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at