3-185789511-A-T

Variant names:

• chr3-185789511-A-T
• rs11705729
• NM_006548.6:c.239+33642T>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+33642T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,976 control chromosomes in the GnomAD database, including 18,172 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 0.45 (18172 hom., cov: 30)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.239+33642T>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+33642T>A		intron_variant	Intron 2 of 15	1	NM_006548.6	ENSP00000371634.3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67856 AN: 151858 Hom.: 18114 Cov.: 30

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.447 AC: 67985 AN: 151976 Hom.: 18172 Cov.: 30 AF XY: 0.443 AC XY: 32924 AN XY: 74262

African (AFR) AF: 0.765 AC: 31725 AN: 41462

American (AMR) AF: 0.319 AC: 4873 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1419 AN: 3466

East Asian (EAS) AF: 0.267 AC: 1377 AN: 5154

South Asian (SAS) AF: 0.435 AC: 2093 AN: 4816

European-Finnish (FIN) AF: 0.315 AC: 3322 AN: 10548

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21741 AN: 67946

Other (OTH) AF: 0.398 AC: 841 AN: 2112

Alfa AF: 0.249 Hom.: 610

Bravo AF: 0.454

Asia WGS AF: 0.425 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.52
PhyloP100		-0.20
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: rs11705729; hg19: chr3-185507299;