NM_006548.6:c.239+29254C>A

Variant names:

• chr3-185793899-G-T
• rs4402960
• NM_006548.6:c.239+29254C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 485 publications found

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]

IGF2BP2 Gene-Disease associations (from GenCC):

• diabetes mellitus, noninsulin-dependent

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006548.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP2	NM_006548.6	MANE Select	c.239+29254C>A		intron	N/A	NP_006539.3
	IGF2BP2	NM_001291869.3		c.239+29254C>A		intron	N/A	NP_001278798.1
	IGF2BP2	NM_001007225.3		c.239+29254C>A		intron	N/A	NP_001007226.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP2	ENST00000382199.7	TSL:1 MANE Select	c.239+29254C>A		intron	N/A	ENSP00000371634.3
	IGF2BP2	ENST00000346192.7	TSL:1	c.239+29254C>A		intron	N/A	ENSP00000320204.5
	IGF2BP2	ENST00000421047.3	TSL:1	c.50+27113C>A		intron	N/A	ENSP00000413787.3

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

African (AFR) AF: 0.521 AC: 21356 AN: 41014

American (AMR) AF: 0.290 AC: 4389 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1276 AN: 5102

South Asian (SAS) AF: 0.430 AC: 2055 AN: 4778

European-Finnish (FIN) AF: 0.317 AC: 3275 AN: 10344

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21601 AN: 67772

Other (OTH) AF: 0.353 AC: 738 AN: 2090

Alfa AF: 0.321 Hom.: 37596

Bravo AF: 0.373

Asia WGS AF: 0.399 AC: 1384 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Diabetes mellitus type 2, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.54
DANN	Benign	0.43
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4402960; hg19: chr3-185511687;