3-185802790-A-G

Variant names:

• chr3-185802790-A-G
• rs6767484
• NM_006548.6:c.239+20363T>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+20363T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,996 control chromosomes in the GnomAD database, including 12,433 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 (12433 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 14 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 = 0.561 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+20363T>C		intron	N/A	NP_006539.3
	IGF2BP2	NM_001291869.3		c.239+20363T>C		intron	N/A	NP_001278798.1
	IGF2BP2	NM_001007225.3		c.239+20363T>C		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+20363T>C		intron	N/A	ENSP00000371634.3
	IGF2BP2	ENST00000346192.7	TSL:1	c.239+20363T>C		intron	N/A	ENSP00000320204.5
	IGF2BP2	ENST00000421047.3	TSL:1	c.50+18222T>C		intron	N/A	ENSP00000413787.3

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59024 AN: 151878 Hom.: 12404 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.389 AC: 59118 AN: 151996 Hom.: 12433 Cov.: 32 AF XY: 0.387 AC XY: 28773 AN XY: 74290

African (AFR) AF: 0.567 AC: 23492 AN: 41448

American (AMR) AF: 0.295 AC: 4509 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1425 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1301 AN: 5162

South Asian (SAS) AF: 0.431 AC: 2070 AN: 4802

European-Finnish (FIN) AF: 0.316 AC: 3330 AN: 10554

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

European-Non Finnish (NFE) AF: 0.318 AC: 21642 AN: 67960

Other (OTH) AF: 0.359 AC: 759 AN: 2116

Alfa AF: 0.289 Hom.: 1570

Bravo AF: 0.388

Asia WGS AF: 0.402 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.079
DANN	Benign	0.69
PhyloP100		-2.2
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: rs6767484; hg19: chr3-185520578; COSMIC: COSV60490902;