rs6769511

chr3-185812502-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006548.6(IGF2BP2):c.239+10651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,088 control chromosomes in the GnomAD database, including 18,368 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 (18368 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2BP2	NM_006548.6	c.239+10651A>G		intron_variant		ENST00000382199.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2BP2	ENST00000382199.7	c.239+10651A>G		intron_variant		1	NM_006548.6	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68129 AN: 151970 Hom.: 18310 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.449 AC: 68258 AN: 152088 Hom.: 18368 Cov.: 32 AF XY: 0.445 AC XY: 33067 AN XY: 74350

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.399

Alfa AF: 0.337 Hom.: 10816

Bravo AF: 0.456

Asia WGS AF: 0.428 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.7
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs6769511; hg19: chr3-185530290;