6-160073377-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000356956.6(IGF2R):ā€‹c.4855A>Gā€‹(p.Arg1619Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,614,202 control chromosomes in the GnomAD database, including 629,117 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.91 ( 63506 hom., cov: 35)
Exomes š‘“: 0.88 ( 565611 hom. )

Consequence

IGF2R
ENST00000356956.6 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02
Variant links:
Genes affected
IGF2R (HGNC:5467): (insulin like growth factor 2 receptor) This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate. The binding sites for each ligand are located on different segments of the protein. This receptor has various functions, including in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. Mutation or loss of heterozygosity of this gene has been association with risk of hepatocellular carcinoma. The orthologous mouse gene is imprinted and shows exclusive expression from the maternal allele; however, imprinting of the human gene may be polymorphic, as only a minority of individuals showed biased expression from the maternal allele (PMID:8267611). [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=8.4388586E-7).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGF2RNM_000876.4 linkuse as main transcriptc.4855A>G p.Arg1619Gly missense_variant 34/48 ENST00000356956.6 NP_000867.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGF2RENST00000356956.6 linkuse as main transcriptc.4855A>G p.Arg1619Gly missense_variant 34/481 NM_000876.4 ENSP00000349437 P1

Frequencies

GnomAD3 genomes
AF:
0.912
AC:
138820
AN:
152232
Hom.:
63442
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.975
Gnomad AMI
AF:
0.910
Gnomad AMR
AF:
0.913
Gnomad ASJ
AF:
0.951
Gnomad EAS
AF:
0.830
Gnomad SAS
AF:
0.889
Gnomad FIN
AF:
0.916
Gnomad MID
AF:
0.968
Gnomad NFE
AF:
0.878
Gnomad OTH
AF:
0.909
GnomAD3 exomes
AF:
0.899
AC:
225927
AN:
251418
Hom.:
101765
AF XY:
0.896
AC XY:
121751
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.977
Gnomad AMR exome
AF:
0.942
Gnomad ASJ exome
AF:
0.949
Gnomad EAS exome
AF:
0.839
Gnomad SAS exome
AF:
0.900
Gnomad FIN exome
AF:
0.908
Gnomad NFE exome
AF:
0.877
Gnomad OTH exome
AF:
0.900
GnomAD4 exome
AF:
0.879
AC:
1285017
AN:
1461852
Hom.:
565611
Cov.:
62
AF XY:
0.880
AC XY:
640053
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.981
Gnomad4 AMR exome
AF:
0.939
Gnomad4 ASJ exome
AF:
0.946
Gnomad4 EAS exome
AF:
0.832
Gnomad4 SAS exome
AF:
0.901
Gnomad4 FIN exome
AF:
0.908
Gnomad4 NFE exome
AF:
0.870
Gnomad4 OTH exome
AF:
0.890
GnomAD4 genome
AF:
0.912
AC:
138943
AN:
152350
Hom.:
63506
Cov.:
35
AF XY:
0.912
AC XY:
67937
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.975
Gnomad4 AMR
AF:
0.914
Gnomad4 ASJ
AF:
0.951
Gnomad4 EAS
AF:
0.831
Gnomad4 SAS
AF:
0.889
Gnomad4 FIN
AF:
0.916
Gnomad4 NFE
AF:
0.878
Gnomad4 OTH
AF:
0.909
Alfa
AF:
0.889
Hom.:
134553
Bravo
AF:
0.916
TwinsUK
AF:
0.869
AC:
3223
ALSPAC
AF:
0.871
AC:
3356
ESP6500AA
AF:
0.969
AC:
4269
ESP6500EA
AF:
0.881
AC:
7575
ExAC
AF:
0.896
AC:
108806
Asia WGS
AF:
0.878
AC:
3053
AN:
3478
EpiCase
AF:
0.884
EpiControl
AF:
0.882

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.041
BayesDel_addAF
Benign
-0.73
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
15
DANN
Benign
0.29
DEOGEN2
Benign
0.052
T;T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.12
.;T
MetaRNN
Benign
8.4e-7
T;T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.30
T
PROVEAN
Benign
3.6
N;.
REVEL
Benign
0.087
Sift
Benign
1.0
T;.
Sift4G
Benign
1.0
T;.
Polyphen
0.0
B;B
Vest4
0.013
MPC
0.52
ClinPred
0.00093
T
GERP RS
4.4
Varity_R
0.056
gMVP
0.70

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: rs629849; hg19: chr6-160494409; API