Variant rs12853546 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003749.3(IRS2):c.2487C>T(p.Pro829Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,549,162 control chromosomes in the GnomAD database, including 47,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4035 hom., cov: 34)

Exomes 𝑓: 0.25 ( 43363 hom. )

Consequence

IRS2
NM_003749.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.75

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=-0.8).

BP6

Variant 13-109783567-G-A is Benign according to our data. Variant chr13-109783567-G-A is described in ClinVar as [Benign]. Clinvar id is 3056733.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3 link	c.2487C>T	p.Pro829Pro	synonymous_variant	Exon 1 of 2	ENST00000375856.5	NP_003740.2	Q9Y4H2Q9P084

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5 link	c.2487C>T	p.Pro829Pro	synonymous_variant	Exon 1 of 2	1	NM_003749.3	ENSP00000365016.3		Q9Y4H2

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34661

AN:

151992

Hom.:

4037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.258

GnomAD3 exomes

AF:

0.236

AC:

33798

AN:

143350

Hom.:

4221

AF XY:

0.242

AC XY:

18810

AN XY:

77582

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.217

Gnomad SAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.246

AC:

344112

AN:

1397052

Hom.:

43363

Cov.:

AF XY:

0.248

AC XY:

170615

AN XY:

688968

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.300

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.228

AC:

34668

AN:

152110

Hom.:

4035

Cov.:

AF XY:

0.228

AC XY:

16917

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.242

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.200

Hom.:

1012

Bravo

AF:

0.223

Asia WGS

AF:

0.250

AC:

868

AN:

3476

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 18, 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

-0.80

CADD

Benign

2.6

DANN

Benign

0.87

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