2-144484555-A-G

Variant names:

• chr2-144484555-A-G
• rs6755392
• NM_014795.4:c.73+32723T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014795.4(ZEB2):​c.73+32723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,908 control chromosomes in the GnomAD database, including 28,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28326 hom., cov: 31)
• Consequence: ZEB2 NM_014795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 12 publications found

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]

ZEB2 Gene-Disease associations (from GenCC):

• Mowat-Wilson syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	NM_014795.4	MANE Select	c.73+32723T>C		intron	N/A	NP_055610.1
	ZEB2	NM_001171653.2		c.73+32723T>C		intron	N/A	NP_001165124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	ENST00000627532.3	TSL:1 MANE Select	c.73+32723T>C		intron	N/A	ENSP00000487174.1
	ZEB2	ENST00000558170.6	TSL:1	c.73+32723T>C		intron	N/A	ENSP00000454157.1
	ZEB2	ENST00000303660.8	TSL:1	c.73+32723T>C		intron	N/A	ENSP00000302501.4

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91325 AN: 151788 Hom.: 28322 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.606

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.601 AC: 91359 AN: 151908 Hom.: 28326 Cov.: 31 AF XY: 0.600 AC XY: 44509 AN XY: 74242

African (AFR) AF: 0.470 AC: 19444 AN: 41396

American (AMR) AF: 0.544 AC: 8304 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2418 AN: 3466

East Asian (EAS) AF: 0.479 AC: 2450 AN: 5120

South Asian (SAS) AF: 0.509 AC: 2448 AN: 4810

European-Finnish (FIN) AF: 0.698 AC: 7373 AN: 10558

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46967 AN: 67970

Other (OTH) AF: 0.601 AC: 1270 AN: 2112

Alfa AF: 0.660 Hom.: 55874

Bravo AF: 0.587

Asia WGS AF: 0.472 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.73
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6755392; hg19: chr2-145242122;