Genetic Variant ZEB2:c.-340+84_-340+86dupGGG (chr2-144520469-A-ACCC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000637267.2(ZEB2):c.-340+84_-340+86dupGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 4 hom., cov: 0)

Exomes 𝑓: 0.014 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

ZEB2
ENST00000637267.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.630

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-144520469-A-ACCC is Benign according to our data. Variant chr2-144520469-A-ACCC is described in ClinVar as [Benign]. Clinvar id is 1675791.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0139 (2714/194778) while in subpopulation AMR AF= 0.017 (194/11400). AF 95% confidence interval is 0.0153. There are 2 homozygotes in gnomad4_exome. There are 1458 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 2714 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB2-AS1	NR_040248.2 link	n.284+190_284+192dupCCC		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ZEB2	ENST00000637267.2 link	c.-340+84_-340+86dupGGG	intron_variant	Intron 1 of 8	5	ENSP00000490293.2	A0A1X7SC99
ZEB2-AS1	ENST00000427278.8 link	n.1011_1013dupCCC	non_coding_transcript_exon_variant	Exon 3 of 3	5
ENSG00000273537	ENST00000621340.1 link	n.20_22dupCCC	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

527

AN:

49310

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00662

Gnomad AMI

AF:

0.0367

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.00240

Gnomad EAS

AF:

0.0174

Gnomad SAS

AF:

0.00691

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0127

GnomAD4 exome

AF:

0.0139

AC:

2714

AN:

194778

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1458

AN XY:

108046

show subpopulations

Gnomad4 AFR exome

AF:

0.00745

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.00554

Gnomad4 EAS exome

AF:

0.0109

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0107

AC:

528

AN:

49348

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

226

AN XY:

21854

show subpopulations

Gnomad4 AFR

AF:

0.00670

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.00240

Gnomad4 EAS

AF:

0.0174

Gnomad4 SAS

AF:

0.00686

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.0126

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZEB2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over