rs6777038

Variant names:

• chr3-185723172-C-T
• rs6777038
• NM_006548.6:c.240-24825G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006548.6(IGF2BP2):​c.240-24825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,188 control chromosomes in the GnomAD database, including 1,115 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 0.11 (1115 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• Publications: 12 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-AS1 (HGNC:32674): (IGF2BP2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.240-24825G>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.240-24825G>A		intron_variant	Intron 2 of 15	1	NM_006548.6	ENSP00000371634.3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16668 AN: 152070 Hom.: 1123 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.110 AC: 16666 AN: 152188 Hom.: 1115 Cov.: 32 AF XY: 0.111 AC XY: 8277 AN XY: 74410

African (AFR) AF: 0.119 AC: 4944 AN: 41500

American (AMR) AF: 0.0870 AC: 1330 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1074 AN: 5180

South Asian (SAS) AF: 0.336 AC: 1619 AN: 4824

European-Finnish (FIN) AF: 0.0499 AC: 529 AN: 10606

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0922 AC: 6268 AN: 68010

Other (OTH) AF: 0.116 AC: 244 AN: 2104

Alfa AF: 0.0996 Hom.: 560

Bravo AF: 0.106

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.83
PhyloP100		2.6
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: rs6777038; hg19: chr3-185440960;