Genetic Variant ZEB2:c.*4845delA (chr2-144384605-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_014795.4(ZEB2):c.*4845delA 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.35

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZEB2	NM_014795.4 link	c.*4845delA		3_prime_UTR_variant	Exon 10 of 10	ENST00000627532.3	NP_055610.1	O60315-1
ZEB2	NM_001171653.2 link	c.*4845delA		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.*4845delA		3_prime_UTR_variant	Exon 10 of 10	1	NM_014795.4	ENSP00000487174.1		O60315-1

Frequencies

GnomAD3 genomes

AF:

0.0336

AC:

4756

AN:

141732

Hom.:

103

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0337

AC:

4771

AN:

141780

Hom.:

105

Cov.:

AF XY:

0.0351

AC XY:

2415

AN XY:

68786

show subpopulations

African (AFR)

AF:

0.0201

AC:

779

AN:

38754

American (AMR)

AF:

0.0438

AC:

621

AN:

14166

Ashkenazi Jewish (ASJ)

AF:

0.0254

AC:

AN:

3310

East Asian (EAS)

AF:

0.106

AC:

529

AN:

4970

South Asian (SAS)

AF:

0.0931

AC:

424

AN:

4552

European-Finnish (FIN)

AF:

0.0414

AC:

354

AN:

8548

Middle Eastern (MID)

AF:

0.0143

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0293

AC:

1888

AN:

64380

Other (OTH)

AF:

0.0372

AC:

AN:

1936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

214

428

641

855

1069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00909

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mowat-Wilson syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=100/0

polymorphism (auto)

(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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chr2-144384605-CT-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over