rs201180901

chr2-144399045-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014795.4(ZEB2):c.2142G>A(p.Pro714=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,613,950 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: ZEB2 NM_014795.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0560

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-144399045-C-T is Benign according to our data. Variant chr2-144399045-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 137948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-144399045-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.056 with no splicing effect.
• BS2: High AC in GnomAd at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.2142G>A	p.Pro714=	synonymous_variant	8/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.2070G>A	p.Pro690=	synonymous_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.2142G>A	p.Pro714=	synonymous_variant	8/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000354 AC: 89 AN: 251142 Hom.: 1 AF XY: 0.000376 AC XY: 51 AN XY: 135712

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00636

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000226 AC: 330 AN: 1461824 Hom.: 1 Cov.: 32 AF XY: 0.000223 AC XY: 162 AN XY: 727218

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00719

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000818

Gnomad4 OTH exome AF: 0.000613

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74314

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000536 Hom.: 0

Bravo AF: 0.000302

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 30, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 30, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 13, 2014	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. -

Mowat-Wilson syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 17, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	9.7
Dann	Benign	0.58

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: rs201180901; hg19: chr2-145156612;