2-144388890-G-GA

Position:

• chr2-144388890-G-GA

Variant summary

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

The NM_014795.4(ZEB2):​c.*560_*561insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 298,326 control chromosomes in the GnomAD database, including 125 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (124 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.34

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 (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.*560_*561insT		3_prime_UTR_variant	10/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.*560_*561insT		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.*560_*561insT		3_prime_UTR_variant	10/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 3798 AN: 117624 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.00308

Gnomad EAS AF: 0.00831

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0367

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0267

GnomAD3 exomes AF: 0.185 AC: 9193 AN: 49662 Hom.: 1 AF XY: 0.190 AC XY: 5062 AN XY: 26678

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.197

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.129 AC: 23364 AN: 180682 Hom.: 1 Cov.: 0 AF XY: 0.128 AC XY: 13101 AN XY: 102746

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0918

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.0323 AC: 3804 AN: 117644 Hom.: 124 Cov.: 32 AF XY: 0.0319 AC XY: 1781 AN XY: 55886

Gnomad4 AFR AF: 0.0874

Gnomad4 AMR AF: 0.0180

Gnomad4 ASJ AF: 0.00308

Gnomad4 EAS AF: 0.00835

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.0265

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mowat-Wilson syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs533637050; hg19: chr2-145146457;