2-144520469-AC-ACCC

Variant names:

• chr2-144520469-A-ACC
• rs1303890891
• ENST00000637267.2:c.-340+85_-340+86dupGG

Variant summary

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

The ENST00000621340.1(ENSG00000273537):​n.21_22dupCC 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 0.31 (1985 hom., cov: 0)
  • Exomes 𝑓: 0.32 (2103 hom.)
  • Failed GnomAD Quality Control
• 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: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 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+191_284+192dupCC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	ENST00000637267.2	TSL:5	c.-340+85_-340+86dupGG		intron	N/A	ENSP00000490293.2	A0A1X7SC99
	ZEB2-AS1	ENST00000427278.8	TSL:5	n.1012_1013dupCC		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000273537	ENST00000621340.1	TSL:6	n.21_22dupCC		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 15152 AN: 48758 Hom.: 1982 Cov.: 0

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.189

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.319 AC: 61379 AN: 192118 Hom.: 2103 Cov.: 0 AF XY: 0.325 AC XY: 34561 AN XY: 106366

African (AFR) AF: 0.227 AC: 1145 AN: 5054

American (AMR) AF: 0.261 AC: 2982 AN: 11430

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 1085 AN: 4234

East Asian (EAS) AF: 0.299 AC: 2341 AN: 7840

South Asian (SAS) AF: 0.360 AC: 13803 AN: 38326

European-Finnish (FIN) AF: 0.303 AC: 2446 AN: 8082

Middle Eastern (MID) AF: 0.247 AC: 156 AN: 632

European-Non Finnish (NFE) AF: 0.321 AC: 34485 AN: 107316

Other (OTH) AF: 0.319 AC: 2936 AN: 9204

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.311 AC: 15167 AN: 48798 Hom.: 1985 Cov.: 0 AF XY: 0.306 AC XY: 6602 AN XY: 21594

African (AFR) AF: 0.268 AC: 2722 AN: 10156

American (AMR) AF: 0.284 AC: 1148 AN: 4046

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 398 AN: 1656

East Asian (EAS) AF: 0.406 AC: 412 AN: 1014

South Asian (SAS) AF: 0.421 AC: 361 AN: 858

European-Finnish (FIN) AF: 0.266 AC: 546 AN: 2054

Middle Eastern (MID) AF: 0.194 AC: 19 AN: 98

European-Non Finnish (NFE) AF: 0.331 AC: 9270 AN: 27988

Other (OTH) AF: 0.306 AC: 191 AN: 624

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		=300/0	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;