2-144387045-GTA-G

Variant names:

• chr2-144387045-GTA-G
• rs143648355
• NM_014795.4:c.*2404_*2405delTA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014795.4(ZEB2):​c.*2404_*2405delTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.026 (147 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.999
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB2	NM_014795.4	c.*2404_*2405delTA		3_prime_UTR_variant	Exon 10 of 10	ENST00000627532.3	NP_055610.1
ZEB2	NM_001171653.2	c.*2404_*2405delTA		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.*2404_*2405delTA		3_prime_UTR_variant	Exon 10 of 10	1	NM_014795.4	ENSP00000487174.1

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3587 AN: 139376 Hom.: 146 Cov.: 0

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00979

Gnomad ASJ AF: 0.000596

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00185

Gnomad FIN AF: 0.00129

Gnomad MID AF: 0.0104

Gnomad NFE AF: 0.000961

Gnomad OTH AF: 0.0195

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

GnomAD4 genome AF: 0.0258 AC: 3603 AN: 139420 Hom.: 147 Cov.: 0 AF XY: 0.0253 AC XY: 1703 AN XY: 67302

African (AFR) AF: 0.0882 AC: 3346 AN: 37928

American (AMR) AF: 0.00972 AC: 135 AN: 13896

Ashkenazi Jewish (ASJ) AF: 0.000596 AC: 2 AN: 3354

East Asian (EAS) AF: 0.00 AC: 0 AN: 4590

South Asian (SAS) AF: 0.00185 AC: 8 AN: 4320

European-Finnish (FIN) AF: 0.00129 AC: 10 AN: 7768

Middle Eastern (MID) AF: 0.0110 AC: 3 AN: 272

European-Non Finnish (NFE) AF: 0.000961 AC: 62 AN: 64510

Other (OTH) AF: 0.0194 AC: 37 AN: 1906

Alfa AF: 0.00 Hom.: 1234

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mowat-Wilson syndrome Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
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: rs143648355; hg19: chr2-145144612; COSMIC: COSV57956543; COSMIC: COSV57956543;