2-216634116-T-G

Position:

• chr2-216634116-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IGFBP2	NM_000597.3	c.442+151T>G		intron_variant		ENST00000233809.9
IGFBP2	NM_001313992.2	c.-57+841T>G		intron_variant
IGFBP2	NM_001313993.2	c.-57+1102T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP2	ENST00000233809.9	c.442+151T>G		intron_variant		1	NM_000597.3	P1
IGFBP2	ENST00000434997.1	c.-57+1102T>G		intron_variant		3
IGFBP2	ENST00000490362.1	n.537+151T>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.321

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

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.306

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

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: rs3770473; hg19: chr2-217498839; COSMIC: COSV52079417;