2-144384605-CT-C

Position:

• chr2-144384605-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014795.4(ZEB2):​c.*4845del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 141,780 control chromosomes in the GnomAD database, including 105 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (105 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.35

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.

• BP6: Variant 2-144384605-CT-C is Benign according to our data. Variant chr2-144384605-CT-C is described in ClinVar as [Benign]. Clinvar id is 331230.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.*4845del		3_prime_UTR_variant	10/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.*4845del		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.*4845del		3_prime_UTR_variant	10/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 4756 AN: 141732 Hom.: 103 Cov.: 29

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0181

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0930

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.0131

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0308

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0337 AC: 4771 AN: 141780 Hom.: 105 Cov.: 29 AF XY: 0.0351 AC XY: 2415 AN XY: 68786

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0931

Gnomad4 FIN AF: 0.0414

Gnomad4 NFE AF: 0.0293

Gnomad4 OTH AF: 0.0372

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mowat-Wilson syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs201661554; hg19: chr2-145142172;