rs770190727

chr2-144399965-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP6_Moderate

The NM_014795.4(ZEB2):c.1222G>A(p.Gly408Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ZEB2 NM_014795.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.17

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 Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ZEB2
• BP6: Variant 2-144399965-C-T is Benign according to our data. Variant chr2-144399965-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 572911.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.1222G>A	p.Gly408Arg	missense_variant	8/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.1150G>A	p.Gly384Arg	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.1222G>A	p.Gly408Arg	missense_variant	8/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251288 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Invitae

Aug 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.020
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.033	T;T;T;T;T;.;T;D;D;T;.;D;T;T;.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.57	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.87	D
Polyphen		0.95, 0.95	.;.;.;.;.;.;.;P;P;.;.;P;P;.;.;.
Vest4		0.86, 0.90, 0.86, 0.88, 0.84
MutPred		0.35		.;.;.;.;.;.;.;Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);.;Gain of helix (P = 0.062);.;.;Gain of helix (P = 0.062);.;
MVP		0.52
MPC		1.6
ClinPred		0.87	D
GERP RS		4.8
Varity_R		0.36
gMVP		0.80

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: rs770190727; hg19: chr2-145157532;