rs12991836

Variant names:

• chr2-144383974-A-C
• rs12991836
• ENST00000639389.1:c.151+12438T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-144383974-A-C
• chr2-144383974-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000639389.1(ZEB2):​c.151+12438T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,056 control chromosomes in the GnomAD database, including 7,952 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 0.31 (7952 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 ENST00000639389.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 27 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000639389.1. 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.*5477T>G		downstream_gene	N/A	NP_055610.1	O60315-1
	ZEB2	NM_001171653.2		c.*5477T>G		downstream_gene	N/A	NP_001165124.1	O60315-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	ENST00000639389.1	TSL:5	c.151+12438T>G		intron	N/A	ENSP00000492572.1	A0A1W2PS25
	ZEB2	ENST00000627532.3	TSL:1 MANE Select	c.*5477T>G		downstream_gene	N/A	ENSP00000487174.1	O60315-1
	ZEB2	ENST00000636471.1	TSL:5	c.*5477T>G		downstream_gene	N/A	ENSP00000490317.1	A0A1B0GV02

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46671 AN: 151938 Hom.: 7951 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.307 AC: 46663 AN: 152056 Hom.: 7952 Cov.: 32 AF XY: 0.311 AC XY: 23119 AN XY: 74318

African (AFR) AF: 0.156 AC: 6497 AN: 41516

American (AMR) AF: 0.331 AC: 5049 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3466

East Asian (EAS) AF: 0.539 AC: 2784 AN: 5166

South Asian (SAS) AF: 0.225 AC: 1087 AN: 4822

European-Finnish (FIN) AF: 0.435 AC: 4595 AN: 10554

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24433 AN: 67946

Other (OTH) AF: 0.313 AC: 661 AN: 2112

Alfa AF: 0.336 Hom.: 30888

Bravo AF: 0.295

Asia WGS AF: 0.352 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12991836;

hg19: chr2-145141541;