chr2-144384605-C-CTTT

Variant names:

• chr2-144384605-C-CTTT
• rs201661554
• NM_014795.4:c.*4843_*4845dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014795.4(ZEB2):​c.*4843_*4845dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000704 in 142,106 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000070 (0 hom., cov: 29)
• Consequence: ZEB2 NM_014795.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	NM_014795.4	MANE Select	c.*4843_*4845dupAAA		3_prime_UTR	Exon 10 of 10	NP_055610.1	O60315-1
	ZEB2	NM_001171653.2		c.*4843_*4845dupAAA		3_prime_UTR	Exon 9 of 9	NP_001165124.1	O60315-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	ENST00000627532.3	TSL:1 MANE Select	c.*4843_*4845dupAAA		3_prime_UTR	Exon 10 of 10	ENSP00000487174.1	O60315-1
	ZEB2	ENST00000636471.1	TSL:5	c.*4843_*4845dupAAA		3_prime_UTR	Exon 10 of 10	ENSP00000490317.1	A0A1B0GV02
	ZEB2	ENST00000636413.1	TSL:5	c.*4843_*4845dupAAA		3_prime_UTR	Exon 9 of 9	ENSP00000490508.1	A0A1B0GVV8

Frequencies

GnomAD3 genomes AF: 0.00000704 AC: 1 AN: 142106 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000704 AC: 1 AN: 142106 Hom.: 0 Cov.: 29 AF XY: 0.0000145 AC XY: 1 AN XY: 68936

African (AFR) AF: 0.00 AC: 0 AN: 38714

American (AMR) AF: 0.00 AC: 0 AN: 14200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3316

East Asian (EAS) AF: 0.00 AC: 0 AN: 4984

South Asian (SAS) AF: 0.00 AC: 0 AN: 4570

European-Finnish (FIN) AF: 0.000116 AC: 1 AN: 8626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64582

Other (OTH) AF: 0.00 AC: 0 AN: 1922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

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

Other links and lift over

dbSNP: rs201661554; hg19: chr2-145142172;