3-185689361-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006548.6(IGF2BP2):c.671A>G(p.Gln224Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGF2BP2 NM_006548.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2BP2	NM_006548.6	c.671A>G	p.Gln224Arg	missense_variant	6/16	ENST00000382199.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2BP2	ENST00000382199.7	c.671A>G	p.Gln224Arg	missense_variant	6/16	1	NM_006548.6	P1
IGF2BP2	ENST00000346192.7	c.671A>G	p.Gln224Arg	missense_variant	6/15	1
IGF2BP2	ENST00000421047.3	c.482A>G	p.Gln161Arg	missense_variant	5/15	1
IGF2BP2	ENST00000457616.6	c.689A>G	p.Gln230Arg	missense_variant	6/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.671A>G (p.Q224R) alteration is located in exon 6 (coding exon 6) of the IGF2BP2 gene. This alteration results from a A to G substitution at nucleotide position 671, causing the glutamine (Q) at amino acid position 224 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
Cadd	Uncertain	25
Dann	Benign	0.93
DEOGEN2	Benign	0.097	T;T;.;.
Eigen	Benign	0.027
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N;.;N;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.63	N;N;N;.
REVEL	Benign	0.25
Sift	Benign	0.83	T;T;T;.
Sift4G	Benign	0.83	T;T;T;T
Polyphen		0.36	B;B;B;P
Vest4		0.69
MutPred		0.46		.;Gain of MoRF binding (P = 0.023);.;.;
MVP		0.88
MPC		1.7
ClinPred		0.63	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-185407149;