chr3-185645612-GCG-ACA

Variant names:

• chr3-185645612-GCG-ACA
• NM_006548.6:c.1717_1719delCGCinsTGT
• IGF2BP2 p.Arg573Cys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_006548.6(IGF2BP2):​c.1717_1719delCGCinsTGT​(p.Arg573Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R573L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGF2BP2 NM_006548.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1717_1719delCGCinsTGT	p.Arg573Cys	missense	N/A	NP_006539.3
	IGF2BP2	NM_001291869.3		c.1735_1737delCGCinsTGT	p.Arg579Cys	missense	N/A	NP_001278798.1	F8W930
	IGF2BP2	NM_001007225.3		c.1588_1590delCGCinsTGT	p.Arg530Cys	missense	N/A	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.1717_1719delCGCinsTGT	p.Arg573Cys	missense	N/A	ENSP00000371634.3	Q9Y6M1-2
	IGF2BP2	ENST00000346192.7	TSL:1	c.1588_1590delCGCinsTGT	p.Arg530Cys	missense	N/A	ENSP00000320204.5	Q9Y6M1-1
	IGF2BP2	ENST00000421047.3	TSL:1	c.1528_1530delCGCinsTGT	p.Arg510Cys	missense	N/A	ENSP00000413787.3	Q9Y6M1-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-185363400;