Variant 13-109782884-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003749.3(IRS2):c.3170G>A(p.Gly1057Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,562,240 control chromosomes in the GnomAD database, including 86,943 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,risk factor (no stars).

Frequency

Genomes: 𝑓 0.29 ( 7081 hom., cov: 32)

Exomes 𝑓: 0.33 ( 79862 hom. )

Consequence

IRS2
NM_003749.3 missense

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:1

Conservation

PhyloP100: 0.425

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.8087368E-4).

BP6

Variant 13-109782884-C-T is Benign according to our data. Variant chr13-109782884-C-T is described in ClinVar as [Benign, risk_factor]. Clinvar id is 8820.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.396 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.3170G>A	p.Gly1057Asp	missense_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.3170G>A	p.Gly1057Asp	missense_variant	1/2	1	NM_003749.3	ENSP00000365016	P1

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43522

AN:

151442

Hom.:

7078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.350

AC:

54931

AN:

156960

Hom.:

10029

AF XY:

0.345

AC XY:

29439

AN XY:

85284

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.401

Gnomad SAS exome

AF:

0.279

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.350

GnomAD4 exome

AF:

0.332

AC:

469031

AN:

1410682

Hom.:

79862

Cov.:

AF XY:

0.331

AC XY:

230790

AN XY:

696988

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.460

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.408

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.324

GnomAD4 genome

AF:

0.287

AC:

43535

AN:

151558

Hom.:

7081

Cov.:

AF XY:

0.291

AC XY:

21534

AN XY:

74054

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.404

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.385

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.330

Hom.:

5352

Bravo

AF:

0.287

TwinsUK

AF:

0.331

AC:

1228

ALSPAC

AF:

0.335

AC:

1292

ESP6500AA

AF:

0.117

AC:

464

ESP6500EA

AF:

0.290

AC:

2312

ExAC

AF:

0.264

AC:

27791

ClinVar

Significance: Benign; risk factor

Submissions summary: Benign:1Other: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). -

Type 2 diabetes mellitus

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Oct 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.30

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.82

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.47

MetaRNN

Benign

0.00038

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.57

REVEL

Benign

0.052

Sift

Benign

0.22

Sift4G

Benign

0.33

Polyphen

0.089

Vest4

0.048

ClinPred

0.0068

GERP RS

2.1

Varity_R

0.033

gMVP

0.37

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