3-185689544-G-A

Variant names:

• chr3-185689544-G-A
• rs182799562
• NM_006548.6:c.488C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006548.6(IGF2BP2):​c.488C>T​(p.Pro163Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000991 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: IGF2BP2 NM_006548.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.52
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11817518).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006548.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP2	NM_006548.6	MANE Select	c.488C>T	p.Pro163Leu	missense	Exon 6 of 16	NP_006539.3
	IGF2BP2	NM_001291869.3		c.506C>T	p.Pro169Leu	missense	Exon 6 of 16	NP_001278798.1	F8W930
	IGF2BP2	NM_001007225.3		c.488C>T	p.Pro163Leu	missense	Exon 6 of 15	NP_001007226.1	Q9Y6M1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP2	ENST00000382199.7	TSL:1 MANE Select	c.488C>T	p.Pro163Leu	missense	Exon 6 of 16	ENSP00000371634.3	Q9Y6M1-2
	IGF2BP2	ENST00000346192.7	TSL:1	c.488C>T	p.Pro163Leu	missense	Exon 6 of 15	ENSP00000320204.5	Q9Y6M1-1
	IGF2BP2	ENST00000421047.3	TSL:1	c.299C>T	p.Pro100Leu	missense	Exon 5 of 15	ENSP00000413787.3	Q9Y6M1-3

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000836 AC: 21 AN: 251306 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000101 AC: 148 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.000114 AC XY: 83 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000120 AC: 133 AN: 1112012

Other (OTH) AF: 0.000116 AC: 7 AN: 60396

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74376

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000153 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	0.0071
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.062
Sift	Benign	0.13	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.28
MVP		0.38
MPC		0.64
ClinPred		0.12	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.38
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs182799562; hg19: chr3-185407332; COSMIC: COSV99063383; COSMIC: COSV99063383;