2-144520469-AC-ACC

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000637267.2(ZEB2):​c.-340+86dupG variant causes a intron 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: ZEB2 ENST00000637267.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630

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

Verdict is Benign. Variant got -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB2-AS1	NR_040248.2	n.284+192dupC		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000637267.2	c.-340+86dupG		intron_variant	Intron 1 of 8	5		ENSP00000490293.2
ZEB2-AS1	ENST00000427278.8	n.1013dupC		non_coding_transcript_exon_variant	Exon 3 of 3	5
ENSG00000273537	ENST00000621340.1	n.22dupC		non_coding_transcript_exon_variant	Exon 1 of 1	6

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

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.281

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

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.290

ClinVar

Not reported in ClinVar

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: rs1303890891; hg19: chr2-145278036;