3-185793899-G-T

Position:

• chr3-185793899-G-T

Variant summary

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

The NM_006548.6(IGF2BP2):​c.239+29254C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 150,916 control chromosomes in the GnomAD database, including 11,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.38 (11250 hom., cov: 29)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 0.107

Genes affected

IGF2BP2 (HGNC:28867): (insulin like growth factor 2 mRNA binding protein 2) This gene encodes a protein that binds the 5' UTR of insulin-like growth factor 2 (IGF2) mRNA and regulates its translation. It plays an important role in metabolism and variation in this gene is associated with susceptibility to diabetes. Alternative splicing and promoter usage results in multiple transcript variants. Related pseudogenes are found on several chromosomes. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2BP2	NM_006548.6	c.239+29254C>A		intron_variant		ENST00000382199.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2BP2	ENST00000382199.7	c.239+29254C>A		intron_variant		1	NM_006548.6	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56604 AN: 150812 Hom.: 11222 Cov.: 29

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.376 AC: 56695 AN: 150916 Hom.: 11250 Cov.: 29 AF XY: 0.374 AC XY: 27590 AN XY: 73676

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.353

Alfa AF: 0.316 Hom.: 17583

Bravo AF: 0.373

Asia WGS AF: 0.399 AC: 1384 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Diabetes mellitus type 2, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.54
DANN	Benign	0.43

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: rs4402960; hg19: chr3-185511687;