chr2-144387062-T-TAC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_014795.4(ZEB2):​c.*2388_*2389insGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00683 in 146,188 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0068 ( 4 hom., cov: 26)
Failed GnomAD Quality Control

Consequence

ZEB2
NM_014795.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.439
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6
Variant 2-144387062-T-TAC is Benign according to our data. Variant chr2-144387062-T-TAC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 331265.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BS2
High AC in GnomAd4 at 999 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZEB2NM_014795.4 linkuse as main transcriptc.*2388_*2389insGT 3_prime_UTR_variant 10/10 ENST00000627532.3
ZEB2NM_001171653.2 linkuse as main transcriptc.*2388_*2389insGT 3_prime_UTR_variant 9/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZEB2ENST00000627532.3 linkuse as main transcriptc.*2388_*2389insGT 3_prime_UTR_variant 10/101 NM_014795.4 P4O60315-1

Frequencies

GnomAD3 genomes
AF:
0.00683
AC:
998
AN:
146106
Hom.:
4
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.0123
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00461
Gnomad ASJ
AF:
0.000876
Gnomad EAS
AF:
0.00281
Gnomad SAS
AF:
0.00343
Gnomad FIN
AF:
0.00220
Gnomad MID
AF:
0.00645
Gnomad NFE
AF:
0.00575
Gnomad OTH
AF:
0.00739
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.00683
AC:
999
AN:
146188
Hom.:
4
Cov.:
26
AF XY:
0.00634
AC XY:
452
AN XY:
71318
show subpopulations
Gnomad4 AFR
AF:
0.0123
Gnomad4 AMR
AF:
0.00460
Gnomad4 ASJ
AF:
0.000876
Gnomad4 EAS
AF:
0.00281
Gnomad4 SAS
AF:
0.00343
Gnomad4 FIN
AF:
0.00220
Gnomad4 NFE
AF:
0.00575
Gnomad4 OTH
AF:
0.00732

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Mowat-Wilson syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023ZEB2: 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.

Other links and lift over

dbSNP: rs886054884; hg19: chr2-145144629; API