2-144387045-G-GTA

Variant names:

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

Variant summary

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

The NM_014795.4(ZEB2):​c.*2404_*2405dupTA 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 0.68 (32149 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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 (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.679 AC: 94566 AN: 139180 Hom.: 32155 Cov.: 0

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.658

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.679 AC: 94571 AN: 139222 Hom.: 32149 Cov.: 0 AF XY: 0.680 AC XY: 45700 AN XY: 67226

African (AFR) AF: 0.555 AC: 21000 AN: 37848

American (AMR) AF: 0.754 AC: 10455 AN: 13868

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2072 AN: 3350

East Asian (EAS) AF: 0.873 AC: 4005 AN: 4588

South Asian (SAS) AF: 0.704 AC: 3029 AN: 4304

European-Finnish (FIN) AF: 0.714 AC: 5538 AN: 7754

Middle Eastern (MID) AF: 0.621 AC: 169 AN: 272

European-Non Finnish (NFE) AF: 0.720 AC: 46405 AN: 64456

Other (OTH) AF: 0.658 AC: 1255 AN: 1908

Alfa AF: 0.601 Hom.: 1234

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided Uncertain:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs143648355; hg19: chr2-145144612;