NM_006548.6:c.239+27549T>C

Variant names:

• chr3-185795604-A-G
• rs7651090
• NM_006548.6:c.239+27549T>C

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+27549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,138 control chromosomes in the GnomAD database, including 12,322 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 0.39 (12322 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71
• Publications: 62 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.239+27549T>C		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+27549T>C		intron_variant	Intron 2 of 15	1	NM_006548.6	ENSP00000371634.3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58865 AN: 152022 Hom.: 12293 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.388 AC: 58959 AN: 152138 Hom.: 12322 Cov.: 32 AF XY: 0.386 AC XY: 28697 AN XY: 74370

African (AFR) AF: 0.561 AC: 23291 AN: 41490

American (AMR) AF: 0.295 AC: 4511 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1424 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1314 AN: 5178

South Asian (SAS) AF: 0.431 AC: 2076 AN: 4818

European-Finnish (FIN) AF: 0.316 AC: 3343 AN: 10584

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21655 AN: 67992

Other (OTH) AF: 0.358 AC: 757 AN: 2112

Alfa AF: 0.342 Hom.: 17746

Bravo AF: 0.386

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.074
DANN	Benign	0.21
PhyloP100		-2.7
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: rs7651090; hg19: chr3-185513392;