rs12991836

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000639389.1	c.151+12438T>G		intron_variant		5		ENSP00000492572

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

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.313

Alfa AF: 0.336 Hom.: 11914

Bravo AF: 0.295

Asia WGS AF: 0.352 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12991836; hg19: chr2-145141541;