chr2-144404027-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014795.4(ZEB2):c.696C>A(p.Tyr232Ter) 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. Y232Y) 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 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZEB2 | NM_014795.4 | c.696C>A | p.Tyr232Ter | stop_gained | 6/10 | ENST00000627532.3 | |
ZEB2 | NM_001171653.2 | c.624C>A | p.Tyr208Ter | stop_gained | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZEB2 | ENST00000627532.3 | c.696C>A | p.Tyr232Ter | 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:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2020 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ZEB2 are known to be pathogenic (PMID: 16053902). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This nonsense change has been observed in individual(s) with Mowat-Wilson syndrome (PMID: 16053902, 27831545, 28501473). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr232*) in the ZEB2 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.