Genetic Variant ZEB2:c.-340+83_-340+86dupGGGG (chr2-144520469-A-ACCCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000621340.1(ENSG00000273537):n.19_22dupCCCC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

ENSG00000273537
ENST00000621340.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.630

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 links:

ZEB2-AS1 (HGNC:37149): (ZEB2 antisense RNA 1) This gene produces a spliced long non-coding RNA which is a natural antisense transcript corresponding to the 5' UTR of zinc finger E-box binding homeobox 2 (ZEB2). It is thought that this transcript may be involved in the regulation of ZEB2 expression, and may play a role in the progression of bladder cancer. [provided by RefSeq, Aug 2015]

ZEB2-AS1 links:

ENSG00000273537 (HGNC:):

ENSG00000273537 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621340.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2-AS1	NR_040248.2		n.284+189_284+192dupCCCC		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZEB2	ENST00000637267.2	TSL:5	c.-340+83_-340+86dupGGGG	intron	N/A	ENSP00000490293.2	A0A1X7SC99
ZEB2-AS1	ENST00000427278.8	TSL:5	n.1010_1013dupCCCC	non_coding_transcript_exon	Exon 3 of 3
ENSG00000273537	ENST00000621340.1	TSL:6	n.19_22dupCCCC	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.000122

AC:

AN:

49370

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000389

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000706

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000864

AC:

AN:

196854

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

109052

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000389

AC:

AN:

5146

American (AMR)

AF:

0.0000865

AC:

AN:

11566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4342

East Asian (EAS)

AF:

0.00

AC:

AN:

8114

South Asian (SAS)

AF:

0.00

AC:

AN:

39460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

636

European-Non Finnish (NFE)

AF:

0.000109

AC:

AN:

109856

Other (OTH)

AF:

0.000212

AC:

AN:

9434

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.287

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000121

AC:

AN:

49408

Hom.:

Cov.:

AF XY:

0.0000914

AC XY:

AN XY:

21874

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000388

AC:

AN:

10304

American (AMR)

AF:

0.00

AC:

AN:

4102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1666

East Asian (EAS)

AF:

0.00

AC:

AN:

1034

South Asian (SAS)

AF:

0.00

AC:

AN:

876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

100

European-Non Finnish (NFE)

AF:

0.0000706

AC:

AN:

28310

Other (OTH)

AF:

0.00

AC:

AN:

634

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00169570), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.383

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.63

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-144520469-AC-ACCCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over