2-144398332-C-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_014795.4(ZEB2):āc.2855G>Cā(p.Arg952Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.0000041 ( 0 hom. )
Consequence
ZEB2
NM_014795.4 missense
NM_014795.4 missense
Scores
3
3
7
Clinical Significance
Conservation
PhyloP100: 7.91
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
Missense variant where missense usually causes diseases, ZEB2
BP4
Computational evidence support a benign effect (MetaRNN=0.36489373).
BP6
Variant 2-144398332-C-G is Benign according to our data. Variant chr2-144398332-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 506473.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2}.
BS2
High AC in GnomAd4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZEB2 | NM_014795.4 | c.2855G>C | p.Arg952Thr | missense_variant | 8/10 | ENST00000627532.3 | |
ZEB2 | NM_001171653.2 | c.2783G>C | p.Arg928Thr | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZEB2 | ENST00000627532.3 | c.2855G>C | p.Arg952Thr | missense_variant | 8/10 | 1 | NM_014795.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251388Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135872
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461674Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727142
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74288
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Mowat-Wilson syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 11, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 04, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T;T;T;T;.;T;T;T;T;.;T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
Polyphen
0.98
.;.;.;.;.;.;.;D;D;.;.;D;D
Vest4
0.75, 0.73, 0.74, 0.71, 0.75
MVP
0.25
MPC
2.6
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at