2-144400025-G-A

Position:

• chr2-144400025-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP6_Moderate

The NM_014795.4(ZEB2):​c.1162C>T​(p.Leu388Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZEB2 NM_014795.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.81

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 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.
• BP6: Variant 2-144400025-G-A is Benign according to our data. Variant chr2-144400025-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 547833.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	c.1162C>T	p.Leu388Phe	missense_variant	8/10	ENST00000627532.3	NP_055610.1
ZEB2	NM_001171653.2	c.1090C>T	p.Leu364Phe	missense_variant	7/9		NP_001165124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000627532.3	c.1162C>T	p.Leu388Phe	missense_variant	8/10	1	NM_014795.4	ENSP00000487174.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mowat-Wilson syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Nov 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T;T;T;T;.;T;T;T;T;.;T;T;T;T;.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	.;.;.;.;D;D;D;.;.;D;D;D;D;T;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	.;.;.;.;.;.;.;M;M;.;.;M;.;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.87	.;.;.;.;.;.;.;.;N;.;N;N;N;.;.;.;.
REVEL	Benign	0.22
Sift	Benign	0.031	.;.;.;.;.;.;.;.;D;.;D;D;D;.;.;.;.
Sift4G	Benign	0.080	.;.;.;.;.;.;.;T;T;.;T;T;T;D;.;.;T
Polyphen		1.0, 1.0	.;.;.;.;.;.;.;D;D;.;.;D;D;.;.;.;.
Vest4		0.65, 0.62, 0.68, 0.58, 0.63, 0.48
MutPred		0.39		.;.;.;.;.;.;.;Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);.;Loss of loop (P = 0.0603);.;.;.;Loss of loop (P = 0.0603);.;
MVP		0.15
MPC		1.6
ClinPred		0.70	D
GERP RS		5.6
Varity_R		0.11
gMVP		0.73

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: rs1553961748; hg19: chr2-145157592;