NM_006548.6:c.239+30057T>G

Variant names:

• chr3-185793096-A-C
• rs16860234
• NM_006548.6:c.239+30057T>G

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+30057T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,070 control chromosomes in the GnomAD database, including 8,488 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 0.32 (8488 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.239+30057T>G		intron_variant	Intron 2 of 15	ENST00000382199.7	NP_006539.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2BP2	ENST00000382199.7	c.239+30057T>G		intron_variant	Intron 2 of 15	1	NM_006548.6	ENSP00000371634.3

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49180 AN: 151952 Hom.: 8478 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.324 AC: 49229 AN: 152070 Hom.: 8488 Cov.: 32 AF XY: 0.322 AC XY: 23949 AN XY: 74346

African (AFR) AF: 0.444 AC: 18398 AN: 41454

American (AMR) AF: 0.224 AC: 3431 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1295 AN: 3464

East Asian (EAS) AF: 0.168 AC: 873 AN: 5184

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4812

European-Finnish (FIN) AF: 0.302 AC: 3196 AN: 10586

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19239 AN: 67966

Other (OTH) AF: 0.306 AC: 646 AN: 2110

Alfa AF: 0.287 Hom.: 25664

Bravo AF: 0.319

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.34
PhyloP100		0.35
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: rs16860234; hg19: chr3-185510884; COSMIC: COSV60492229;