Variant 6-160096449-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000876.4(IGF2R):c.6666C>T(p.Leu2222Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 1,609,300 control chromosomes in the GnomAD database, including 13,537 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.

Frequency

Genomes: 𝑓 0.14 ( 2320 hom., cov: 33)

Exomes 𝑓: 0.091 ( 11217 hom. )

Consequence

IGF2R
NM_000876.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.154

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4 linkuse as main transcript	c.6666C>T	p.Leu2222Leu	synonymous_variant	45/48	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.6666C>T	p.Leu2222Leu	synonymous_variant	45/48	1	NM_000876.4	ENSP00000349437.1		P11717

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21551

AN:

152036

Hom.:

2304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.0765

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.150

AC:

37338

AN:

248114

Hom.:

4816

AF XY:

0.141

AC XY:

18931

AN XY:

134120

show subpopulations

Gnomad AFR exome

AF:

0.242

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.416

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.0846

Gnomad NFE exome

AF:

0.0643

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0908

AC:

132317

AN:

1457146

Hom.:

11217

Cov.:

AF XY:

0.0921

AC XY:

66721

AN XY:

724536

show subpopulations

Gnomad4 AFR exome

AF:

0.243

Gnomad4 AMR exome

AF:

0.296

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.424

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.0840

Gnomad4 NFE exome

AF:

0.0608

Gnomad4 OTH exome

AF:

0.0989

GnomAD4 genome

AF:

0.142

AC:

21603

AN:

152154

Hom.:

2320

Cov.:

AF XY:

0.145

AC XY:

10806

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.0765

Gnomad4 NFE

AF:

0.0655

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.0838

Hom.:

1897

Bravo

AF:

0.156

Asia WGS

AF:

0.305

AC:

1061

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.5

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 28

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