chr3-185807411-A-G

Variant names:

• chr3-185807411-A-G
• rs13060777
• NM_006548.6:c.239+15742T>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+15742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,116 control chromosomes in the GnomAD database, including 5,076 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 0.26 (5076 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 11 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.239+15742T>C		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+15742T>C		intron_variant	Intron 2 of 15	1	NM_006548.6	ENSP00000371634.3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39101 AN: 151998 Hom.: 5074 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.257 AC: 39130 AN: 152116 Hom.: 5076 Cov.: 32 AF XY: 0.258 AC XY: 19158 AN XY: 74374

African (AFR) AF: 0.279 AC: 11584 AN: 41472

American (AMR) AF: 0.181 AC: 2775 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3466

East Asian (EAS) AF: 0.158 AC: 821 AN: 5184

South Asian (SAS) AF: 0.273 AC: 1315 AN: 4820

European-Finnish (FIN) AF: 0.292 AC: 3087 AN: 10568

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17425 AN: 67982

Other (OTH) AF: 0.245 AC: 518 AN: 2116

Alfa AF: 0.251 Hom.: 2952

Bravo AF: 0.248

Asia WGS AF: 0.252 AC: 876 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.84
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: rs13060777; hg19: chr3-185525199;