Variant 6-160024661-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_000876.4(IGF2R):c.603C>T(p.Ser201Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00682 in 1,614,012 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 61 hom. )

Consequence

IGF2R
NM_000876.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.43

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 6-160024661-C-T is Benign according to our data. Variant chr6-160024661-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657098.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-160024661-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.43 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00632 (962/152202) while in subpopulation NFE AF= 0.00635 (432/68010). AF 95% confidence interval is 0.00586. There are 11 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 962 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4 linkuse as main transcript	c.603C>T	p.Ser201Ser	synonymous_variant	5/48	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.603C>T	p.Ser201Ser	synonymous_variant	5/48	1	NM_000876.4	ENSP00000349437.1	P11717
IGF2R	ENST00000676781.1 linkuse as main transcript	n.603C>T		non_coding_transcript_exon_variant	5/49			ENSP00000504419.1	A0A7I2YQS7
IGF2R	ENST00000677704.1 linkuse as main transcript	n.603C>T		non_coding_transcript_exon_variant	5/49			ENSP00000503314.1	A0A7I2V381

Frequencies

GnomAD3 genomes

AF:

0.00632

AC:

961

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00635

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00700

AC:

1760

AN:

251480

Hom.:

AF XY:

0.00678

AC XY:

922

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.0370

Gnomad NFE exome

AF:

0.00729

Gnomad OTH exome

AF:

0.00586

GnomAD4 exome

AF:

0.00688

AC:

10053

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00654

AC XY:

4753

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00128

Gnomad4 FIN exome

AF:

0.0360

Gnomad4 NFE exome

AF:

0.00682

Gnomad4 OTH exome

AF:

0.00571

GnomAD4 genome

AF:

0.00632

AC:

962

AN:

152202

Hom.:

Cov.:

AF XY:

0.00788

AC XY:

586

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0386

Gnomad4 NFE

AF:

0.00635

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00594

Hom.:

Bravo

AF:

0.00352

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00529

EpiControl

AF:

0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

IGF2R: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.6

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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