rs12105918

Positions:

• chr2-144450626-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014795.4(ZEB2):​c.74-20600A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 152,270 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.062 (344 hom., cov: 32)
• Consequence: ZEB2 NM_014795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZEB2	NM_014795.4	c.74-20600A>G		intron_variant		ENST00000627532.3
ZEB2	NM_001171653.2	c.74-20600A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZEB2	ENST00000627532.3	c.74-20600A>G		intron_variant		1	NM_014795.4	P4

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9405 AN: 152152 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.0712

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0618 AC: 9409 AN: 152270 Hom.: 344 Cov.: 32 AF XY: 0.0621 AC XY: 4621 AN XY: 74464

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0844

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0598

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0633 Hom.: 496

Bravo AF: 0.0620

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12105918; hg19: chr2-145208193;