chr2-144389415-G-GA

Position:

• chr2-144389415-G-GA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_014795.4(ZEB2):​c.*35_*36insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,574,642 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.27

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 -6 ACMG points.

• BP6: Variant 2-144389415-G-GA is Benign according to our data. Variant chr2-144389415-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 331297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.*35_*36insT		3_prime_UTR_variant	10/10	ENST00000627532.3
ZEB2	NM_001171653.2	c.*35_*36insT		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.*35_*36insT		3_prime_UTR_variant	10/10	1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.000113 AC: 17 AN: 150060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000584

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.0000996

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000593

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000402 AC: 572 AN: 1424466 Hom.: 0 Cov.: 30 AF XY: 0.000365 AC XY: 259 AN XY: 710192

Gnomad4 AFR exome AF: 0.000153

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.00180

Gnomad4 SAS exome AF: 0.000340

Gnomad4 FIN exome AF: 0.000285

Gnomad4 NFE exome AF: 0.000397

Gnomad4 OTH exome AF: 0.000321

GnomAD4 genome AF: 0.000113 AC: 17 AN: 150176 Hom.: 0 Cov.: 32 AF XY: 0.000164 AC XY: 12 AN XY: 73222

Gnomad4 AFR AF: 0.000171

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000586

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.0000996

Gnomad4 NFE AF: 0.0000593

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000144

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mowat-Wilson syndrome Benign:1

Likely benign, 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)		0.020		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: rs567229506; hg19: chr2-145146982;