chr2-144466053-C-T

Variant names:

• chr2-144466053-C-T
• rs13382811
• NM_014795.4:c.74-36027G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014795.4(ZEB2):​c.74-36027G>A variant causes a intron change. The variant allele was found at a frequency of 0.208 in 152,144 control chromosomes in the GnomAD database, including 3,896 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3896 hom., cov: 32)
• Consequence: ZEB2 NM_014795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78
• Publications: 28 publications found

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 Gene-Disease associations (from GenCC):

• Mowat-Wilson syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	NM_014795.4	MANE Select	c.74-36027G>A		intron	N/A	NP_055610.1	O60315-1
	ZEB2	NM_001171653.2		c.74-36027G>A		intron	N/A	NP_001165124.1	O60315-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	ENST00000627532.3	TSL:1 MANE Select	c.74-36027G>A		intron	N/A	ENSP00000487174.1	O60315-1
	ZEB2	ENST00000558170.6	TSL:1	c.74-36027G>A		intron	N/A	ENSP00000454157.1	O60315-1
	ZEB2	ENST00000303660.8	TSL:1	c.74-36027G>A		intron	N/A	ENSP00000302501.4	A0JP08

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31678 AN: 152026 Hom.: 3893 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.213

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31711 AN: 152144 Hom.: 3896 Cov.: 32 AF XY: 0.208 AC XY: 15444 AN XY: 74360

African (AFR) AF: 0.322 AC: 13352 AN: 41494

American (AMR) AF: 0.281 AC: 4301 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1286 AN: 5178

South Asian (SAS) AF: 0.116 AC: 559 AN: 4828

European-Finnish (FIN) AF: 0.165 AC: 1748 AN: 10586

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9504 AN: 67984

Other (OTH) AF: 0.216 AC: 456 AN: 2114

Alfa AF: 0.156 Hom.: 6618

Bravo AF: 0.226

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.88
PhyloP100		5.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13382811; hg19: chr2-145223620;