chr3-185824915-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006548.6(IGF2BP2):​c.46G>A​(p.Ala16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IGF2BP2
NM_006548.6 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.282
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16125995).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IGF2BP2NM_006548.6 linkuse as main transcriptc.46G>A p.Ala16Thr missense_variant 1/16 ENST00000382199.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IGF2BP2ENST00000382199.7 linkuse as main transcriptc.46G>A p.Ala16Thr missense_variant 1/161 NM_006548.6 P1Q9Y6M1-2
IGF2BP2ENST00000346192.7 linkuse as main transcriptc.46G>A p.Ala16Thr missense_variant 1/151 Q9Y6M1-1
IGF2BP2ENST00000457616.6 linkuse as main transcriptc.46G>A p.Ala16Thr missense_variant 1/165
IGF2BP2ENST00000466476.1 linkuse as main transcript upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000565
AC:
8
AN:
1415676
Hom.:
0
Cov.:
31
AF XY:
0.00000426
AC XY:
3
AN XY:
703502
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000148
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000184
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 08, 2021The c.46G>A (p.A16T) alteration is located in exon 1 (coding exon 1) of the IGF2BP2 gene. This alteration results from a G to A substitution at nucleotide position 46, causing the alanine (A) at amino acid position 16 to be replaced by a threonine (T). 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
0.11
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.092
T;T;.
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.72
T;T;T
M_CAP
Pathogenic
0.33
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.49
N;.;N
MutationTaster
Benign
0.60
D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.40
N;N;N
REVEL
Benign
0.073
Sift
Benign
0.068
T;T;T
Sift4G
Benign
0.25
T;T;T
Polyphen
0.87
P;B;P
Vest4
0.13
MutPred
0.48
Gain of glycosylation at T15 (P = 0.0396);Gain of glycosylation at T15 (P = 0.0396);Gain of glycosylation at T15 (P = 0.0396);
MVP
0.31
MPC
0.94
ClinPred
0.22
T
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.056
gMVP
0.35

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764179905; hg19: chr3-185542703; API