rs797046122
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_014795.4(ZEB2):c.674C>A(p.Ser225Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S225S) has been classified as Likely benign. 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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZEB2 | NM_014795.4 | c.674C>A | p.Ser225Ter | stop_gained | 6/10 | ENST00000627532.3 | |
ZEB2 | NM_001171653.2 | c.602C>A | p.Ser201Ter | stop_gained | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZEB2 | ENST00000627532.3 | c.674C>A | p.Ser225Ter | stop_gained | 6/10 | 1 | NM_014795.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Mowat-Wilson syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 07, 2014 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2016 | The S225X pathogenic variant in the ZEB2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The S225X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret S225X as a pathogenic variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at