2-144520469-AC-ACCC

Variant names:

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

Variant summary

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

The ENST00000637267.2(ZEB2):​c.-340+85_-340+86dupGG 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 0.31 (1985 hom., cov: 0)
  • Exomes 𝑓: 0.32 (2103 hom.)
  • Failed GnomAD Quality Control
• 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: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZEB2-AS1	NR_040248.2	n.284+191_284+192dupCC		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZEB2	ENST00000637267.2	c.-340+85_-340+86dupGG		intron_variant	Intron 1 of 8	5		ENSP00000490293.2
ZEB2-AS1	ENST00000427278.8	n.1012_1013dupCC		non_coding_transcript_exon_variant	Exon 3 of 3	5
ENSG00000273537	ENST00000621340.1	n.21_22dupCC		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 15152 AN: 48758 Hom.: 1982 Cov.: 0 FAILED QC

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

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.299

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.319

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

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.306

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;