2-144520469-AC-ACCCC

Variant names:

• chr2-144520469-A-ACCC
• rs1303890891
• ENST00000637267.2:c.-340+84_-340+86dupGGG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000621340.1(ENSG00000273537):​n.20_22dupCCC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (4 hom., cov: 0)
  • Exomes 𝑓: 0.014 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000273537 ENST00000621340.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 2-144520469-A-ACCC is Benign according to our data. Variant chr2-144520469-A-ACCC is described in ClinVar as Benign. ClinVar VariationId is 1675791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

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+190_284+192dupCCC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZEB2	ENST00000637267.2	TSL:5	c.-340+84_-340+86dupGGG		intron	N/A	ENSP00000490293.2	A0A1X7SC99
	ZEB2-AS1	ENST00000427278.8	TSL:5	n.1011_1013dupCCC		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000273537	ENST00000621340.1	TSL:6	n.20_22dupCCC		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 527 AN: 49310 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00662

Gnomad AMI AF: 0.0367

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00240

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.00691

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0127

GnomAD4 exome AF: 0.0139 AC: 2714 AN: 194778 Hom.: 2 Cov.: 0 AF XY: 0.0135 AC XY: 1458 AN XY: 108046

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00745 AC: 38 AN: 5098

American (AMR) AF: 0.0170 AC: 194 AN: 11400

Ashkenazi Jewish (ASJ) AF: 0.00554 AC: 24 AN: 4336

East Asian (EAS) AF: 0.0109 AC: 87 AN: 8018

South Asian (SAS) AF: 0.0102 AC: 400 AN: 39176

European-Finnish (FIN) AF: 0.0143 AC: 117 AN: 8196

Middle Eastern (MID) AF: 0.00313 AC: 2 AN: 638

European-Non Finnish (NFE) AF: 0.0159 AC: 1727 AN: 108592

Other (OTH) AF: 0.0134 AC: 125 AN: 9324

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0107 AC: 528 AN: 49348 Hom.: 4 Cov.: 0 AF XY: 0.0103 AC XY: 226 AN XY: 21854

African (AFR) AF: 0.00670 AC: 69 AN: 10300

American (AMR) AF: 0.0132 AC: 54 AN: 4100

Ashkenazi Jewish (ASJ) AF: 0.00240 AC: 4 AN: 1666

East Asian (EAS) AF: 0.0174 AC: 18 AN: 1032

South Asian (SAS) AF: 0.00686 AC: 6 AN: 874

European-Finnish (FIN) AF: 0.0125 AC: 26 AN: 2074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 100

European-Non Finnish (NFE) AF: 0.0117 AC: 332 AN: 28268

Other (OTH) AF: 0.0126 AC: 8 AN: 634

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63
Mutation Taster		=300/0	polymorphism

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;