chr2-144388890-GA-G

Position:

• chr2-144388890-GA-G

Variant summary

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

The NM_014795.4(ZEB2):​c.*560del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 297,450 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 32)
  • Exomes 𝑓: 0.14 (0 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: GnomAdExome4 highest subpopulation (AMR) 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.*560del		3_prime_UTR_variant	10/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.*560del		3_prime_UTR_variant	9/9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 601 AN: 117746 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00413

Gnomad ASJ AF: 0.000342

Gnomad EAS AF: 0.000978

Gnomad SAS AF: 0.000761

Gnomad FIN AF: 0.00854

Gnomad MID AF: 0.00455

Gnomad NFE AF: 0.00729

Gnomad OTH AF: 0.00517

GnomAD3 exomes AF: 0.201 AC: 9968 AN: 49662 Hom.: 0 AF XY: 0.199 AC XY: 5309 AN XY: 26678

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.184

Gnomad SAS exome AF: 0.201

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.135 AC: 24322 AN: 179684 Hom.: 0 Cov.: 0 AF XY: 0.132 AC XY: 13444 AN XY: 102086

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.00512 AC: 603 AN: 117766 Hom.: 2 Cov.: 32 AF XY: 0.00509 AC XY: 285 AN XY: 55952

Gnomad4 AFR AF: 0.00265

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.000342

Gnomad4 EAS AF: 0.000982

Gnomad4 SAS AF: 0.00102

Gnomad4 FIN AF: 0.00854

Gnomad4 NFE AF: 0.00729

Gnomad4 OTH AF: 0.00513

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)		0.0		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: rs533637050; hg19: chr2-145146457;