chr3-185763280-C-T

Variant names:

• chr3-185763280-C-T
• rs4686692
• NM_006548.6:c.239+59873G>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+59873G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,194 control chromosomes in the GnomAD database, including 57,429 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 0.87 (57429 hom., cov: 31)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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+59873G>A		intron	N/A	NP_006539.3
	IGF2BP2	NM_001291869.3		c.239+59873G>A		intron	N/A	NP_001278798.1
	IGF2BP2	NM_001007225.3		c.239+59873G>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+59873G>A		intron	N/A	ENSP00000371634.3
	IGF2BP2	ENST00000346192.7	TSL:1	c.239+59873G>A		intron	N/A	ENSP00000320204.5
	IGF2BP2	ENST00000421047.3	TSL:1	c.50+57732G>A		intron	N/A	ENSP00000413787.3

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131536 AN: 152076 Hom.: 57368 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.865 AC: 131657 AN: 152194 Hom.: 57429 Cov.: 31 AF XY: 0.869 AC XY: 64661 AN XY: 74408

African (AFR) AF: 0.964 AC: 40024 AN: 41532

American (AMR) AF: 0.888 AC: 13575 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3027 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5175 AN: 5180

South Asian (SAS) AF: 0.928 AC: 4481 AN: 4830

European-Finnish (FIN) AF: 0.830 AC: 8796 AN: 10602

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53754 AN: 67986

Other (OTH) AF: 0.852 AC: 1797 AN: 2110

Alfa AF: 0.842 Hom.: 45187

Bravo AF: 0.872

Asia WGS AF: 0.969 AC: 3366 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.27
PhyloP100		-0.30
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: rs4686692; hg19: chr3-185481068;