Variant 6-160073896-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000876.4(IGF2R):c.5087A>G(p.Gln1696Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000992 in 1,614,212 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts 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: 𝑓 0.0040 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 8 hom. )

Consequence

IGF2R
NM_000876.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.14

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:

IGF2R (HGNC:):

IGF2R links:

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=0.010492653).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00399 (608/152344) while in subpopulation AFR AF= 0.0126 (525/41584). AF 95% confidence interval is 0.0117. There are 3 homozygotes in gnomad4. There are 273 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 608 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4 linkuse as main transcript	c.5087A>G	p.Gln1696Arg	missense_variant	35/48	ENST00000356956.6	NP_000867.3	P11717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6 linkuse as main transcript	c.5087A>G	p.Gln1696Arg	missense_variant	35/48	1	NM_000876.4	ENSP00000349437.1		P11717

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

609

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00130

AC:

328

AN:

251432

Hom.:

AF XY:

0.00109

AC XY:

148

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000536

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000680

AC:

994

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000597

AC XY:

434

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000302

Gnomad4 OTH exome

AF:

0.00184

GnomAD4 genome

AF:

0.00399

AC:

608

AN:

152344

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

273

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00484

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0123

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00155

AC:

188

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

.;T

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.16

N;.

REVEL

Benign

0.18

Sift

Benign

0.47

T;.

Sift4G

Benign

0.20

T;.

Polyphen

0.98

D;D

Vest4

0.28

MVP

0.54

MPC

0.66

ClinPred

0.041

GERP RS

5.6

Varity_R

0.31

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.

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