NM_014795.4:c.3141G>C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2
The NM_014795.4(ZEB2):c.3141G>C(p.Arg1047Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1047K) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
ZEB2
NM_014795.4 missense
NM_014795.4 missense
Scores
6
6
7
Clinical Significance
Conservation
PhyloP100: 0.541
Publications
2 publications found
Genes affected
ZEB2 (HGNC:14881): (zinc finger E-box binding homeobox 2) The protein encoded by this gene is a member of the Zfh1 family of 2-handed zinc finger/homeodomain proteins. It is located in the nucleus and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs. Mutations in this gene are associated with Hirschsprung disease/Mowat-Wilson syndrome. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jan 2010]
ZEB2 Gene-Disease associations (from GenCC):
- Mowat-Wilson syndromeInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM1
In a hotspot region, there are 10 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_014795.4
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mowat-Wilson syndrome Uncertain:1
Jun 16, 2014
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T;.;T;D;D;T;.;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;.;.;T;T;T;.;.;T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;.;M;M;.;.;M;.
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
.;.;.;.;.;.;.;.;D;.;D;D;.
REVEL
Benign
Sift
Pathogenic
.;.;.;.;.;.;.;.;D;.;D;D;.
Sift4G
Pathogenic
.;.;.;.;.;.;.;D;D;.;D;D;D
Polyphen
0.99
.;.;.;.;.;.;.;D;D;.;.;D;D
Vest4
0.87, 0.84, 0.92, 0.90, 0.94
MutPred
0.42
.;.;.;.;.;.;.;Loss of MoRF binding (P = 0.0491);Loss of MoRF binding (P = 0.0491);Loss of MoRF binding (P = 0.0491);.;Loss of MoRF binding (P = 0.0491);.;
MVP
0.64
MPC
1.8
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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