2-144384605-C-CT

Position:

• chr2-144384605-C-CT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014795.4(ZEB2):​c.*4845_*4846insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 142,098 control chromosomes in the GnomAD database, including 940 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.11 (940 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.*4845_*4846insA		3_prime_UTR_variant	10/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.*4845_*4846insA		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.*4845_*4846insA		3_prime_UTR_variant	10/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.115 AC: 16323 AN: 142046 Hom.: 939 Cov.: 29

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0882

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.116

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: 0.115 AC: 16340 AN: 142098 Hom.: 940 Cov.: 29 AF XY: 0.115 AC XY: 7964 AN XY: 68972

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0875

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.117

Bravo AF: 0.109

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mowat-Wilson syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs201661554; hg19: chr2-145142172;