3-185764830-T-C

Variant names:

• chr3-185764830-T-C
• rs6763887
• NM_006548.6:c.239+58323A>G

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+58323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,046 control chromosomes in the GnomAD database, including 38,922 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 0.71 (38922 hom., cov: 31)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.239+58323A>G		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+58323A>G		intron_variant	Intron 2 of 15	1	NM_006548.6	ENSP00000371634.3

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107108 AN: 151928 Hom.: 38859 Cov.: 31

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.705 AC: 107232 AN: 152046 Hom.: 38922 Cov.: 31 AF XY: 0.700 AC XY: 52017 AN XY: 74304

African (AFR) AF: 0.869 AC: 36041 AN: 41494

American (AMR) AF: 0.594 AC: 9071 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2841 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2019 AN: 5164

South Asian (SAS) AF: 0.679 AC: 3271 AN: 4816

European-Finnish (FIN) AF: 0.620 AC: 6539 AN: 10554

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45124 AN: 67972

Other (OTH) AF: 0.704 AC: 1487 AN: 2112

Alfa AF: 0.673 Hom.: 111100

Bravo AF: 0.705

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.61
PhyloP100		-0.92
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: rs6763887; hg19: chr3-185482618;