chr2-144388936-GA-G

Position:

• chr2-144388936-GA-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014795.4(ZEB2):​c.*514del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 365,770 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (1 hom.)
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 351 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.*514del		3_prime_UTR_variant	10/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.*514del		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.*514del		3_prime_UTR_variant	10/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 350 AN: 145602 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00782

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00219

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00304

GnomAD4 exome AF: 0.00507 AC: 1117 AN: 220112 Hom.: 1 Cov.: 0 AF XY: 0.00479 AC XY: 606 AN XY: 126458

Gnomad4 AFR exome AF: 0.0158

Gnomad4 AMR exome AF: 0.00837

Gnomad4 ASJ exome AF: 0.00317

Gnomad4 EAS exome AF: 0.00606

Gnomad4 SAS exome AF: 0.00411

Gnomad4 FIN exome AF: 0.00460

Gnomad4 NFE exome AF: 0.00473

Gnomad4 OTH exome AF: 0.00426

GnomAD4 genome AF: 0.00241 AC: 351 AN: 145658 Hom.: 0 Cov.: 32 AF XY: 0.00250 AC XY: 177 AN XY: 70678

Gnomad4 AFR AF: 0.00783

Gnomad4 AMR AF: 0.00219

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000111

Gnomad4 NFE AF: 0.0000152

Gnomad4 OTH AF: 0.00300

Bravo AF: 0.00292

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: rs558553086; hg19: chr2-145146503;