11-32434752-G-C
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_024426.6(WT1):c.609C>G(p.Asn203Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. N203N) has been classified as Benign.
Frequency
Consequence
NM_024426.6 missense
Scores
Clinical Significance
Conservation
Publications
- Denys-Drash syndromeInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P
- Wilms tumor 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
- familial idiopathic steroid-resistant nephrotic syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Frasier syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WT1 | ENST00000452863.10 | c.609C>G | p.Asn203Lys | missense_variant | Exon 1 of 10 | 1 | NM_024426.6 | ENSP00000415516.5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460498Hom.: 0 Cov.: 43 AF XY: 0.00000138 AC XY: 1AN XY: 726576 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 Uncertain:1
In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a WT1-related disease. This sequence change replaces asparagine with lysine at codon 198 of the WT1 protein (p.Asn198Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at