rs587784564

Variant names:

• chr2-144398858-G-A
• rs587784564
• NM_014795.4:c.2329C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-144398858-G-A
• chr2-144398858-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014795.4(ZEB2):​c.2329C>T​(p.His777Tyr) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZEB2 NM_014795.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.92

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB2	NM_014795.4	c.2329C>T	p.His777Tyr	missense_variant	Exon 8 of 10	ENST00000627532.3	NP_055610.1
ZEB2	NM_001171653.2	c.2257C>T	p.His753Tyr	missense_variant	Exon 7 of 9		NP_001165124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000627532.3	c.2329C>T	p.His777Tyr	missense_variant	Exon 8 of 10	1	NM_014795.4	ENSP00000487174.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mowat-Wilson syndrome Uncertain:1

Jan 23, 2014

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;T;T;T;T;.;T;T;T;T;.;T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;.;.;.;D;D;D;.;.;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;.;.;.;.;.;.;L;L;.;.;L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.4	.;.;.;.;.;.;.;.;N;.;N;N;.
REVEL	Uncertain	0.36
Sift	Benign	0.099	.;.;.;.;.;.;.;.;T;.;T;T;.
Sift4G	Benign	0.64	.;.;.;.;.;.;.;T;T;.;T;T;T
Polyphen		0.96	.;.;.;.;.;.;.;D;D;.;.;D;D
Vest4		0.88, 0.75, 0.85, 0.76, 0.79
MutPred		0.16		.;.;.;.;.;.;.;Gain of phosphorylation at H777 (P = 0.0295);Gain of phosphorylation at H777 (P = 0.0295);Gain of phosphorylation at H777 (P = 0.0295);.;Gain of phosphorylation at H777 (P = 0.0295);.;
MVP		0.28
MPC		1.6
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.19
gMVP		0.38

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

Other links and lift over

dbSNP: rs587784564; hg19: chr2-145156425;