2-144384605-C-CTT

Position:

• chr2-144384605-C-CTT

Variant summary

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

The NM_014795.4(ZEB2):​c.*4845_*4846insAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 142,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35

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 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.*4845_*4846insAA		3_prime_UTR_variant	10/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.*4845_*4846insAA		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.*4845_*4846insAA		3_prime_UTR_variant	10/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.000239 AC: 34 AN: 142102 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000232

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000108

Gnomad OTH AF: 0.00

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: 0.000239 AC: 34 AN: 142102 Hom.: 0 Cov.: 29 AF XY: 0.000261 AC XY: 18 AN XY: 68932

Gnomad4 AFR AF: 0.000542

Gnomad4 AMR AF: 0.000282

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000232

Gnomad4 NFE AF: 0.000108

Gnomad4 OTH AF: 0.00

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: rs201661554; hg19: chr2-145142172;