Variant 6-160084175-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000876.4(IGF2R):c.6059A>G(p.Asn2020Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0618 in 1,608,400 control chromosomes in the GnomAD database, including 6,251 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.061 ( 639 hom., cov: 32)

Exomes 𝑓: 0.062 ( 5612 hom. )

Consequence

IGF2R
NM_000876.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.76

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]

IGF2R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046558976).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4 link	c.6059A>G	p.Asn2020Ser	missense_variant	40/48	ENST00000356956.6	NP_000867.3	P11717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6 link	c.6059A>G	p.Asn2020Ser	missense_variant	40/48	1	NM_000876.4	ENSP00000349437.1		P11717

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9208

AN:

152032

Hom.:

634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0689

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0495

Gnomad OTH

AF:

0.0559

GnomAD3 exomes

AF:

0.104

AC:

26079

AN:

250810

Hom.:

2735

AF XY:

0.0974

AC XY:

13213

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.00795

Gnomad EAS exome

AF:

0.325

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0757

Gnomad NFE exome

AF:

0.0475

Gnomad OTH exome

AF:

0.0756

GnomAD4 exome

AF:

0.0620

AC:

90248

AN:

1456250

Hom.:

5612

Cov.:

AF XY:

0.0624

AC XY:

45214

AN XY:

724766

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.00808

Gnomad4 EAS exome

AF:

0.315

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.0749

Gnomad4 NFE exome

AF:

0.0443

Gnomad4 OTH exome

AF:

0.0608

GnomAD4 genome

AF:

0.0606

AC:

9216

AN:

152150

Hom.:

639

Cov.:

AF XY:

0.0643

AC XY:

4779

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0689

Gnomad4 NFE

AF:

0.0495

Gnomad4 OTH

AF:

0.0610

Alfa

AF:

0.0525

Hom.:

898

Bravo

AF:

0.0673

TwinsUK

AF:

0.0394

AC:

146

ALSPAC

AF:

0.0451

AC:

174

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.0417

AC:

359

ExAC

AF:

0.0973

AC:

11807

Asia WGS

AF:

0.215

AC:

750

AN:

3478

EpiCase

AF:

0.0403

EpiControl

AF:

0.0383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.39

.;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.39

N;.

REVEL

Benign

0.11

Sift

Benign

0.23

T;.

Sift4G

Benign

0.45

T;.

Polyphen

0.0

B;B

Vest4

0.022

MPC

0.32

ClinPred

0.012

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.068

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over