3-185818435-G-T

Variant names:

• chr3-185818435-G-T
• rs6444082
• NM_006548.6:c.239+4718C>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+4718C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,992 control chromosomes in the GnomAD database, including 14,345 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 (14345 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 15 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.239+4718C>A		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+4718C>A		intron_variant	Intron 2 of 15	1	NM_006548.6	ENSP00000371634.3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58734 AN: 151874 Hom.: 14292 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.387 AC: 58856 AN: 151992 Hom.: 14345 Cov.: 32 AF XY: 0.386 AC XY: 28653 AN XY: 74274

African (AFR) AF: 0.705 AC: 29205 AN: 41444

American (AMR) AF: 0.268 AC: 4086 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5168

South Asian (SAS) AF: 0.359 AC: 1728 AN: 4818

European-Finnish (FIN) AF: 0.280 AC: 2954 AN: 10568

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17286 AN: 67958

Other (OTH) AF: 0.329 AC: 696 AN: 2114

Alfa AF: 0.291 Hom.: 9726

Bravo AF: 0.392

Asia WGS AF: 0.370 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6444082; hg19: chr3-185536223;