Variant rs8191904 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000876.4(IGF2R):c.5495G>A(p.Arg1832His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,452,580 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0092 ( 25 hom., cov: 33)

Exomes 𝑓: 0.00086 ( 14 hom. )

Consequence

IGF2R
NM_000876.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0340

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029729903).

BP6

Variant 6-160079596-G-A is Benign according to our data. Variant chr6-160079596-G-A is described in ClinVar as [Benign]. Clinvar id is 709060.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00923 (1406/152318) while in subpopulation AFR AF= 0.0319 (1325/41552). AF 95% confidence interval is 0.0305. There are 25 homozygotes in gnomad4. There are 639 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1406 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4 link	c.5495G>A	p.Arg1832His	missense_variant	38/48	ENST00000356956.6	NP_000867.3	P11717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6 link	c.5495G>A	p.Arg1832His	missense_variant	38/48	1	NM_000876.4	ENSP00000349437.1		P11717

Frequencies

GnomAD3 genomes

AF:

0.00914

AC:

1391

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

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:

0.000147

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00255

AC:

396

AN:

155224

Hom.:

AF XY:

0.00186

AC XY:

157

AN XY:

84260

show subpopulations

Gnomad AFR exome

AF:

0.0310

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.000229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000712

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000755

Gnomad OTH exome

AF:

0.000319

GnomAD4 exome

AF:

0.000861

AC:

1120

AN:

1300262

Hom.:

Cov.:

AF XY:

0.000787

AC XY:

501

AN XY:

636640

show subpopulations

Gnomad4 AFR exome

AF:

0.0326

Gnomad4 AMR exome

AF:

0.00185

Gnomad4 ASJ exome

AF:

0.000305

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000331

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000641

Gnomad4 OTH exome

AF:

0.00197

GnomAD4 genome

AF:

0.00923

AC:

1406

AN:

152318

Hom.:

Cov.:

AF XY:

0.00858

AC XY:

639

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0319

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00742

Hom.:

755

Bravo

AF:

0.0104

ESP6500AA

AF:

0.0288

AC:

127

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00289

AC:

351

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.72

.;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.27

PROVEAN

Benign

0.13

N;.

REVEL

Benign

0.036

Sift

Benign

0.62

T;.

Sift4G

Benign

0.46

T;.

Polyphen

0.0020

B;B

Vest4

0.071

MVP

0.27

MPC

0.50

ClinPred

0.0064

GERP RS

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.40

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over