chr2-144466053-C-T

Position:

• chr2-144466053-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZEB2	NM_014795.4	c.74-36027G>A		intron_variant		ENST00000627532.3	NP_055610.1
ZEB2	NM_001171653.2	c.74-36027G>A		intron_variant			NP_001165124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000627532.3	c.74-36027G>A		intron_variant		1	NM_014795.4	ENSP00000487174	P4

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

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.216

Alfa AF: 0.141 Hom.: 2288

Bravo AF: 0.226

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.88

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: rs13382811; hg19: chr2-145223620;