Genetic Variant ZEB2:c.*35delT (chr2-144389415-GA-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_014795.4(ZEB2):c.*35delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000746 in 1,580,884 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

ZEB2
NM_014795.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.27

Publications

0 publications found

Variant links:

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

ZEB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB2	NM_014795.4 link	c.*35delT		3_prime_UTR_variant	Exon 10 of 10	ENST00000627532.3	NP_055610.1	O60315-1
ZEB2	NM_001171653.2 link	c.*35delT		3_prime_UTR_variant	Exon 9 of 9		NP_001165124.1	O60315-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000627532.3 link	c.*35delT		3_prime_UTR_variant	Exon 10 of 10	1	NM_014795.4	ENSP00000487174.1		O60315-1

Frequencies

GnomAD3 genomes

AF:

0.000147

AC:

AN:

150064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000441

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000190

AC:

AN:

231308

AF XY:

0.000160

show subpopulations

Gnomad AFR exome

AF:

0.000395

Gnomad AMR exome

AF:

0.000779

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000107

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.0000671

AC:

AN:

1430704

Hom.:

Cov.:

AF XY:

0.0000757

AC XY:

AN XY:

713092

show subpopulations

African (AFR)

AF:

0.000304

AC:

AN:

32846

American (AMR)

AF:

0.000763

AC:

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25856

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39488

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85496

European-Finnish (FIN)

AF:

0.0000759

AC:

AN:

52686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1084728

Other (OTH)

AF:

0.0000842

AC:

AN:

59358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000146

AC:

AN:

150180

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73228

show subpopulations

African (AFR)

AF:

0.000439

AC:

AN:

40970

American (AMR)

AF:

0.000264

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67410

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=100/0

polymorphism

(source)

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

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chr2-144389415-GA-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over