2-216650048-C-T

Position:

• chr2-216650048-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000597.3(IGFBP2):​c.443-10509C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 152,288 control chromosomes in the GnomAD database, including 63 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 0.025 (63 hom., cov: 33)
• Consequence: IGFBP2 NM_000597.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453

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=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3809/152288) while in subpopulation NFE AF= 0.0408 (2776/68032). AF 95% confidence interval is 0.0395. There are 63 homozygotes in gnomad4. There are 1724 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 63 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP2	NM_000597.3	c.443-10509C>T		intron_variant		ENST00000233809.9
IGFBP2	NM_001313992.2	c.-56-10509C>T		intron_variant
IGFBP2	NM_001313993.2	c.-56-10509C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP2	ENST00000233809.9	c.443-10509C>T		intron_variant		1	NM_000597.3	P1
IGFBP2	ENST00000434997.1	c.-56-10509C>T		intron_variant		3
IGFBP2	ENST00000490362.1	n.538-10509C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3810 AN: 152170 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.00731

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0278

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0250 AC: 3809 AN: 152288 Hom.: 63 Cov.: 33 AF XY: 0.0231 AC XY: 1724 AN XY: 74472

Gnomad4 AFR AF: 0.00729

Gnomad4 AMR AF: 0.0180

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.0278

Gnomad4 NFE AF: 0.0408

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0242 Hom.: 15

Bravo AF: 0.0234

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.75

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: rs9341156; hg19: chr2-217514771;