2-144520469-AC-ACC

Variant names:

• chr2-144520469-A-AC
• rs1303890891
• ENST00000637267.2:c.-340+86dupG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000621340.1(ENSG00000273537):​n.22dupC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (2053 hom., cov: 0)
  • Exomes 𝑓: 0.27 (4124 hom.)
• Consequence: ENSG00000273537 ENST00000621340.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 0 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-AS1 (HGNC:37149): (ZEB2 antisense RNA 1) This gene produces a spliced long non-coding RNA which is a natural antisense transcript corresponding to the 5' UTR of zinc finger E-box binding homeobox 2 (ZEB2). It is thought that this transcript may be involved in the regulation of ZEB2 expression, and may play a role in the progression of bladder cancer. [provided by RefSeq, Aug 2015]

ENSG00000273537 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621340.1. 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-AS1	NR_040248.2		n.284+192dupC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	ENST00000637267.2	TSL:5	c.-340+86dupG		intron	N/A	ENSP00000490293.2	A0A1X7SC99
	ZEB2-AS1	ENST00000427278.8	TSL:5	n.1013dupC		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000273537	ENST00000621340.1	TSL:6	n.22dupC		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 14419 AN: 49234 Hom.: 2053 Cov.: 0

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.293

GnomAD4 exome AF: 0.267 AC: 49719 AN: 185984 Hom.: 4124 Cov.: 0 AF XY: 0.257 AC XY: 26449 AN XY: 102940

African (AFR) AF: 0.167 AC: 836 AN: 4998

American (AMR) AF: 0.226 AC: 2501 AN: 11068

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1591 AN: 4230

East Asian (EAS) AF: 0.105 AC: 809 AN: 7692

South Asian (SAS) AF: 0.174 AC: 6380 AN: 36618

European-Finnish (FIN) AF: 0.277 AC: 2190 AN: 7904

Middle Eastern (MID) AF: 0.342 AC: 213 AN: 622

European-Non Finnish (NFE) AF: 0.315 AC: 32689 AN: 103926

Other (OTH) AF: 0.281 AC: 2510 AN: 8926

GnomAD4 genome AF: 0.293 AC: 14424 AN: 49272 Hom.: 2053 Cov.: 0 AF XY: 0.291 AC XY: 6352 AN XY: 21808

African (AFR) AF: 0.206 AC: 2118 AN: 10262

American (AMR) AF: 0.272 AC: 1113 AN: 4092

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 696 AN: 1658

East Asian (EAS) AF: 0.0878 AC: 91 AN: 1036

South Asian (SAS) AF: 0.161 AC: 141 AN: 874

European-Finnish (FIN) AF: 0.307 AC: 635 AN: 2070

Middle Eastern (MID) AF: 0.439 AC: 43 AN: 98

European-Non Finnish (NFE) AF: 0.330 AC: 9321 AN: 28240

Other (OTH) AF: 0.290 AC: 184 AN: 634

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63
Mutation Taster		=299/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1303890891; hg19: chr2-145278036;