Genetic Variant ENST00000637267.2:c.-340+82_-340+86dupGGGGG (chr2-144520469-A-ACCCCC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The ENST00000637267.2(ZEB2):c.-340+82_-340+86dupGGGGG variant causes a intron 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 0.00018 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ZEB2
ENST00000637267.2 intron

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:

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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 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637267.2. 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+188_284+192dupCCCCC		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZEB2	ENST00000637267.2	TSL:5	c.-340+82_-340+86dupGGGGG	intron	N/A	ENSP00000490293.2	A0A1X7SC99
ZEB2-AS1	ENST00000427278.8	TSL:5	n.1009_1013dupCCCCC	non_coding_transcript_exon	Exon 3 of 3
ENSG00000273537	ENST00000621340.1	TSL:6	n.18_22dupCCCCC	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.000182

AC:

AN:

49376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00654

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:

0.000247

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

196900

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

109074

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

5152

American (AMR)

AF:

0.00

AC:

AN:

11570

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:

39462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

638

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

109888

Other (OTH)

AF:

0.00

AC:

AN:

9432

⚠️ 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: 0.242

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000182

AC:

AN:

49414

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

AN XY:

21878

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10308

American (AMR)

AF:

0.00

AC:

AN:

4104

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:

0.000247

AC:

AN:

28310

Other (OTH)

AF:

0.00

AC:

AN:

634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over