Variant chr2-144389978-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate

The NM_014795.4(ZEB2):c.3118C>T(p.His1040Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZEB2
NM_014795.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 10.0

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZEB2. . Gene score misZ 3.9433 (greater than the threshold 3.09). Trascript score misZ 5.6227 (greater than threshold 3.09). GenCC has associacion of gene with Mowat-Wilson syndrome.

PP5

Variant 2-144389978-G-A is Pathogenic according to our data. Variant chr2-144389978-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 496685.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZEB2	NM_014795.4 linkuse as main transcript	c.3118C>T	p.His1040Tyr	missense_variant	10/10	ENST00000627532.3	NP_055610.1
ZEB2	NM_001171653.2 linkuse as main transcript	c.3046C>T	p.His1016Tyr	missense_variant	9/9		NP_001165124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000627532.3 linkuse as main transcript	c.3118C>T	p.His1040Tyr	missense_variant	10/10	1	NM_014795.4	ENSP00000487174	P4	O60315-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mowat-Wilson syndrome

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Oct 13, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;T;T;T;.;T;D;D;T;.;D;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

.;.;.;.;T;T;T;.;.;T;T;T;T

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.60

D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.15

.;.;.;.;.;.;.;N;N;.;.;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Pathogenic

-5.3

.;.;.;.;.;.;.;.;D;.;D;D;.

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

.;.;.;.;.;.;.;.;D;.;D;D;.

Sift4G

Pathogenic

0.0

.;.;.;.;.;.;.;D;D;.;D;D;D

Polyphen

0.98

.;.;.;.;.;.;.;D;D;.;.;D;D

Vest4

0.69, 0.59, 0.77, 0.57, 0.78

MutPred

0.31

.;.;.;.;.;.;.;Loss of methylation at K1039 (P = 0.0679);Loss of methylation at K1039 (P = 0.0679);Loss of methylation at K1039 (P = 0.0679);.;Loss of methylation at K1039 (P = 0.0679);.;

MVP

0.38

MPC

2.3

ClinPred

0.97

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over