chr2-144387045-G-GTATA

Position:

• chr2-144387045-G-GTATA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_014795.4(ZEB2):​c.*2405_*2406insTATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (7 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.999

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 -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0069 (961/139364) while in subpopulation EAS AF= 0.0262 (120/4586). AF 95% confidence interval is 0.0224. There are 7 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 961 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.*2405_*2406insTATA		3_prime_UTR_variant	10/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.*2405_*2406insTATA		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.*2405_*2406insTATA		3_prime_UTR_variant	10/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.00690 AC: 961 AN: 139322 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00706

Gnomad ASJ AF: 0.00388

Gnomad EAS AF: 0.0263

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00347

Gnomad NFE AF: 0.00626

Gnomad OTH AF: 0.00740

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: 0.00690 AC: 961 AN: 139364 Hom.: 7 Cov.: 0 AF XY: 0.00690 AC XY: 464 AN XY: 67268

Gnomad4 AFR AF: 0.00701

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00388

Gnomad4 EAS AF: 0.0262

Gnomad4 SAS AF: 0.00790

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00627

Gnomad4 OTH AF: 0.00735

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143648355; hg19: chr2-145144612;