rs9341189

Positions:

• chr2-216656105-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.443-4452T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 152,182 control chromosomes in the GnomAD database, including 136 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 0.035 (136 hom., cov: 32)
• Consequence: IGFBP2 NM_000597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP2	NM_000597.3	c.443-4452T>G		intron_variant		ENST00000233809.9	NP_000588.3
IGFBP2	NM_001313992.2	c.-56-4452T>G		intron_variant			NP_001300921.1
IGFBP2	NM_001313993.2	c.-56-4452T>G		intron_variant			NP_001300922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP2	ENST00000233809.9	c.443-4452T>G		intron_variant		1	NM_000597.3	ENSP00000233809.4
IGFBP2	ENST00000434997.1	c.-56-4452T>G		intron_variant		3		ENSP00000401698.1
IGFBP2	ENST00000490362.1	n.538-4452T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5361 AN: 152064 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0352 AC: 5362 AN: 152182 Hom.: 136 Cov.: 32 AF XY: 0.0360 AC XY: 2677 AN XY: 74402

Gnomad4 AFR AF: 0.00860

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0434

Gnomad4 FIN AF: 0.0560

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0479 Hom.: 45

Bravo AF: 0.0304

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.83

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: rs9341189; hg19: chr2-217520828;