rs16860216

Variant names:

• chr3-185771094-G-A
• rs16860216
• NM_006548.6:c.239+52059C>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+52059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,946 control chromosomes in the GnomAD database, including 7,192 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 0.30 (7192 hom., cov: 31)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733
• Publications: 16 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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 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+52059C>T		intron	N/A	NP_006539.3
	IGF2BP2	NM_001291869.3		c.239+52059C>T		intron	N/A	NP_001278798.1
	IGF2BP2	NM_001007225.3		c.239+52059C>T		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+52059C>T		intron	N/A	ENSP00000371634.3
	IGF2BP2	ENST00000346192.7	TSL:1	c.239+52059C>T		intron	N/A	ENSP00000320204.5
	IGF2BP2	ENST00000421047.3	TSL:1	c.50+49918C>T		intron	N/A	ENSP00000413787.3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44803 AN: 151828 Hom.: 7178 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.295 AC: 44852 AN: 151946 Hom.: 7192 Cov.: 31 AF XY: 0.293 AC XY: 21791 AN XY: 74270

African (AFR) AF: 0.431 AC: 17857 AN: 41438

American (AMR) AF: 0.209 AC: 3190 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3468

East Asian (EAS) AF: 0.167 AC: 859 AN: 5152

South Asian (SAS) AF: 0.268 AC: 1287 AN: 4810

European-Finnish (FIN) AF: 0.284 AC: 2992 AN: 10550

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16616 AN: 67948

Other (OTH) AF: 0.273 AC: 577 AN: 2112

Alfa AF: 0.253 Hom.: 6594

Bravo AF: 0.293

Asia WGS AF: 0.236 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.1
DANN	Benign	0.66
PhyloP100		0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs16860216; hg19: chr3-185488882;