2-144384605-CTTT-CT

Variant names:

• chr2-144384605-CTT-C
• rs201661554
• NM_014795.4:c.*4844_*4845delAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014795.4(ZEB2):​c.*4844_*4845delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 142,110 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00037 (1 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB2	NM_014795.4	c.*4844_*4845delAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000627532.3	NP_055610.1
ZEB2	NM_001171653.2	c.*4844_*4845delAA		3_prime_UTR_variant	Exon 9 of 9		NP_001165124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000627532.3	c.*4844_*4845delAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_014795.4	ENSP00000487174.1

Frequencies

GnomAD3 genomes AF: 0.000380 AC: 54 AN: 142058 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0107

Gnomad FIN AF: 0.000116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000465

Gnomad OTH AF: 0.000520

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

GnomAD4 genome AF: 0.000373 AC: 53 AN: 142110 Hom.: 1 Cov.: 29 AF XY: 0.000464 AC XY: 32 AN XY: 68982

African (AFR) AF: 0.00 AC: 0 AN: 38788

American (AMR) AF: 0.00 AC: 0 AN: 14210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3316

East Asian (EAS) AF: 0.00 AC: 0 AN: 4970

South Asian (SAS) AF: 0.0105 AC: 48 AN: 4554

European-Finnish (FIN) AF: 0.000116 AC: 1 AN: 8610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.0000465 AC: 3 AN: 64554

Other (OTH) AF: 0.000515 AC: 1 AN: 1942

Alfa AF: 0.00 Hom.: 37

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism

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: rs201661554; hg19: chr2-145142172;