chr2-144387045-G-GTA

Position:

• chr2-144387045-G-GTA

Variant summary

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

The NM_014795.4(ZEB2):​c.*2405_*2406insTA 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 0.68 (32149 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.679 AC: 94566 AN: 139180 Hom.: 32155 Cov.: 0

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.658

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: 0.679 AC: 94571 AN: 139222 Hom.: 32149 Cov.: 0 AF XY: 0.680 AC XY: 45700 AN XY: 67226

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.658

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

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;