2-144399231-G-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_014795.4(ZEB2):c.1956C>A(p.Tyr652*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_014795.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Mowat-Wilson syndrome Pathogenic:2
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Inborn genetic diseases Pathogenic:1
The p.Y652* pathogenic mutation (also known as c.1956C>A), located in coding exon 7 of the ZEB2 gene, results from a C to A substitution at nucleotide position 1956. This changes the amino acid from a tyrosine to a stop codon within coding exon 7. This mutation has been described in a 35-week stillborn male fetus with features consistent with Mowat-Wilson syndrome, including dysmorphic facial features, hypospadias, ventricular septal defect, short corpus callosum, and Hirschsprung disease (Spaggiari E et al. Eur J Med Genet, 2013 Jun;56:297-300). A different nucleotide substitution at the same nucleotide position (c.1956C>G), also resulting in the p.Y652* nonsense mutation, was described in a 19-year-old Indonesian male with Mowat-Wilson syndrome, whose features included severe intellectual disability, hypotonia, onset of seizures at age 2 years, repetitive hand movements, and facial dysmorphism (Mundhofir FE et al. Case Rep Genet, 2012 Dec;2012:949507). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at