2-216634116-T-G

Variant names:

• chr2-216634116-T-G
• rs3770473
• NM_000597.3:c.442+151T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000597.3(IGFBP2):​c.442+151T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,290,544 control chromosomes in the GnomAD database, including 71,055 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 0.32 (8122 hom., cov: 33)
  • Exomes 𝑓: 0.33 (62933 hom.)
• Consequence: IGFBP2 NM_000597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 9 publications found

Genes affected

IGFBP2 (HGNC:5471): (insulin like growth factor binding protein 2) The protein encoded by this gene is one of six similar proteins that bind insulin-like growth factors I and II (IGF-I and IGF-II). The encoded protein can be secreted into the bloodstream, where it binds IGF-I and IGF-II with high affinity, or it can remain intracellular, interacting with many different ligands. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the patient. Several transcript variants, one encoding a secreted isoform and the others encoding nonsecreted isoforms, have been found for this gene. [provided by RefSeq, Sep 2015]

ENSG00000303260 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP2	NM_000597.3	c.442+151T>G		intron_variant	Intron 1 of 3	ENST00000233809.9	NP_000588.3
IGFBP2	NM_001313992.2	c.-57+841T>G		intron_variant	Intron 1 of 3		NP_001300921.1
IGFBP2	NM_001313993.2	c.-57+1102T>G		intron_variant	Intron 1 of 3		NP_001300922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP2	ENST00000233809.9	c.442+151T>G		intron_variant	Intron 1 of 3	1	NM_000597.3	ENSP00000233809.4
IGFBP2	ENST00000434997.1	c.-57+1102T>G		intron_variant	Intron 1 of 2	3		ENSP00000401698.1
IGFBP2	ENST00000490362.1	n.537+151T>G		intron_variant	Intron 1 of 1	2
ENSG00000303260	ENST00000793255.1	n.113+2219A>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49101 AN: 151968 Hom.: 8103 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.329 AC: 374130 AN: 1138458 Hom.: 62933 AF XY: 0.328 AC XY: 181942 AN XY: 554504

African (AFR) AF: 0.273 AC: 6352 AN: 23268

American (AMR) AF: 0.361 AC: 6297 AN: 17434

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 3917 AN: 17188

East Asian (EAS) AF: 0.475 AC: 13698 AN: 28842

South Asian (SAS) AF: 0.318 AC: 17963 AN: 56566

European-Finnish (FIN) AF: 0.356 AC: 10284 AN: 28888

Middle Eastern (MID) AF: 0.219 AC: 709 AN: 3242

European-Non Finnish (NFE) AF: 0.327 AC: 299617 AN: 915406

Other (OTH) AF: 0.321 AC: 15293 AN: 47624

GnomAD4 genome AF: 0.323 AC: 49145 AN: 152086 Hom.: 8122 Cov.: 33 AF XY: 0.327 AC XY: 24306 AN XY: 74318

African (AFR) AF: 0.287 AC: 11917 AN: 41498

American (AMR) AF: 0.345 AC: 5270 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2213 AN: 5150

South Asian (SAS) AF: 0.319 AC: 1534 AN: 4816

European-Finnish (FIN) AF: 0.385 AC: 4064 AN: 10568

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22301 AN: 67982

Other (OTH) AF: 0.306 AC: 646 AN: 2108

Alfa AF: 0.335 Hom.: 1106

Bravo AF: 0.317

Asia WGS AF: 0.360 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		-1.6
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: rs3770473; hg19: chr2-217498839; COSMIC: COSV52079417;