rs9859406

Variant names:

• chr3-185816694-G-A
• rs9859406
• NM_006548.6:c.239+6459C>T

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+6459C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,046 control chromosomes in the GnomAD database, including 18,339 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 0.45 (18339 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 20 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP2	NM_006548.6	MANE Select	c.239+6459C>T		intron	N/A	NP_006539.3
	IGF2BP2	NM_001291869.3		c.239+6459C>T		intron	N/A	NP_001278798.1	F8W930
	IGF2BP2	NM_001007225.3		c.239+6459C>T		intron	N/A	NP_001007226.1	Q9Y6M1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP2	ENST00000382199.7	TSL:1 MANE Select	c.239+6459C>T		intron	N/A	ENSP00000371634.3	Q9Y6M1-2
	IGF2BP2	ENST00000346192.7	TSL:1	c.239+6459C>T		intron	N/A	ENSP00000320204.5	Q9Y6M1-1
	IGF2BP2	ENST00000421047.3	TSL:1	c.50+4318C>T		intron	N/A	ENSP00000413787.3	Q9Y6M1-3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68032 AN: 151928 Hom.: 18281 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.448 AC: 68161 AN: 152046 Hom.: 18339 Cov.: 32 AF XY: 0.444 AC XY: 33029 AN XY: 74326

African (AFR) AF: 0.771 AC: 31991 AN: 41498

American (AMR) AF: 0.319 AC: 4875 AN: 15266

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

East Asian (EAS) AF: 0.268 AC: 1388 AN: 5176

South Asian (SAS) AF: 0.433 AC: 2090 AN: 4822

European-Finnish (FIN) AF: 0.308 AC: 3254 AN: 10556

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21702 AN: 67950

Other (OTH) AF: 0.401 AC: 845 AN: 2108

Alfa AF: 0.415 Hom.: 2550

Bravo AF: 0.455

Asia WGS AF: 0.427 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.023
DANN	Benign	0.28
PhyloP100		-1.4
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: rs9859406; hg19: chr3-185534482;