Variant rs4773092 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000375856.5(IRS2):c.2448T>C(p.Cys816=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,548,250 control chromosomes in the GnomAD database, including 267,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.60 ( 27103 hom., cov: 34)

Exomes 𝑓: 0.58 ( 239991 hom. )

Consequence

IRS2
ENST00000375856.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.540

Variant links:

Genes affected

IRS2 (HGNC:6126): (insulin receptor substrate 2) This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment. [provided by RefSeq, Jul 2008]

IRS2 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 (BayesDel_noAF=-0.92).

BP6

Variant 13-109783606-A-G is Benign according to our data. Variant chr13-109783606-A-G is described in ClinVar as [Benign]. Clinvar id is 3059034.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS2	NM_003749.3 linkuse as main transcript	c.2448T>C	p.Cys816=	synonymous_variant	1/2	ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5 linkuse as main transcript	c.2448T>C	p.Cys816=	synonymous_variant	1/2	1	NM_003749.3	ENSP00000365016	P1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90337

AN:

151834

Hom.:

27071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.606

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.651

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.449

Gnomad SAS

AF:

0.501

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.474

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.562

GnomAD3 exomes

AF:

0.587

AC:

87024

AN:

148290

Hom.:

25906

AF XY:

0.580

AC XY:

46376

AN XY:

79996

show subpopulations

Gnomad AFR exome

AF:

0.602

Gnomad AMR exome

AF:

0.693

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.467

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.589

Gnomad OTH exome

AF:

0.569

GnomAD4 exome

AF:

0.585

AC:

816240

AN:

1396298

Hom.:

239991

Cov.:

AF XY:

0.582

AC XY:

400698

AN XY:

687964

show subpopulations

Gnomad4 AFR exome

AF:

0.604

Gnomad4 AMR exome

AF:

0.687

Gnomad4 ASJ exome

AF:

0.617

Gnomad4 EAS exome

AF:

0.490

Gnomad4 SAS exome

AF:

0.503

Gnomad4 FIN exome

AF:

0.609

Gnomad4 NFE exome

AF:

0.590

Gnomad4 OTH exome

AF:

0.569

GnomAD4 genome

AF:

0.595

AC:

90418

AN:

151952

Hom.:

27103

Cov.:

AF XY:

0.595

AC XY:

44184

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.606

Gnomad4 AMR

AF:

0.652

Gnomad4 ASJ

AF:

0.621

Gnomad4 EAS

AF:

0.448

Gnomad4 SAS

AF:

0.501

Gnomad4 FIN

AF:

0.604

Gnomad4 NFE

AF:

0.594

Gnomad4 OTH

AF:

0.559

Alfa

AF:

0.590

Hom.:

34524

Bravo

AF:

0.601

Asia WGS

AF:

0.477

AC:

1665

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IRS2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.81

DANN

Benign

0.43

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