Variant 6-160010723-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP5_ModerateBS2

The NM_000876.4(IGF2R):c.451C>T(p.His151Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,611,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

IGF2R
NM_000876.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.11

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 Likely_benign. Variant got -2 ACMG points.

PP5

Variant 6-160010723-C-T is Pathogenic according to our data. Variant chr6-160010723-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 929753.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4 linkuse as main transcript	c.451C>T	p.His151Tyr	missense_variant	4/48	ENST00000356956.6	NP_000867.3	P11717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGF2R	ENST00000356956.6 linkuse as main transcript	c.451C>T	p.His151Tyr	missense_variant	4/48	1	NM_000876.4	ENSP00000349437.1	P11717
IGF2R	ENST00000676781.1 linkuse as main transcript	n.451C>T		non_coding_transcript_exon_variant	4/49			ENSP00000504419.1	A0A7I2YQS7
IGF2R	ENST00000677704.1 linkuse as main transcript	n.451C>T		non_coding_transcript_exon_variant	4/49			ENSP00000503314.1	A0A7I2V381

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251410

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1459742

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726340

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Premature ovarian failure

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano

Mar 02, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.20

Sift

Benign

0.22

T;.

Sift4G

Uncertain

0.0050

D;.

Polyphen

1.0

D;D

Vest4

0.80

MutPred

0.67

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.64

MPC

0.40

ClinPred

0.76

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over