dbSNP rs41275080: IRS2:c.*1820A>G (chr13-109754484-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003749.3(IRS2):c.*1820A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 200,156 control chromosomes in the GnomAD database, including 1,694 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 0.079 ( 1594 hom., cov: 33)

Exomes 𝑓: 0.016 ( 100 hom. )

Consequence

IRS2
NM_003749.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0650

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3 link	c.*1820A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5 link	c.*1820A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

11764

AN:

148368

Hom.:

1592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000877

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000699

Gnomad OTH

AF:

0.0611

GnomAD4 exome

AF:

0.0162

AC:

839

AN:

51670

Hom.:

100

Cov.:

AF XY:

0.0140

AC XY:

337

AN XY:

24060

show subpopulations

African (AFR)

AF:

0.283

AC:

653

AN:

2304

American (AMR)

AF:

0.0237

AC:

AN:

1476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3276

East Asian (EAS)

AF:

0.00

AC:

AN:

7858

South Asian (SAS)

AF:

0.00

AC:

AN:

474

European-Finnish (FIN)

AF:

0.00

AC:

AN:

346

Middle Eastern (MID)

AF:

0.0191

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000988

AC:

AN:

31374

Other (OTH)

AF:

0.0268

AC:

114

AN:

4248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0794

AC:

11788

AN:

148486

Hom.:

1594

Cov.:

AF XY:

0.0757

AC XY:

5465

AN XY:

72202

show subpopulations

African (AFR)

AF:

0.278

AC:

11222

AN:

40428

American (AMR)

AF:

0.0272

AC:

392

AN:

14434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5024

South Asian (SAS)

AF:

0.000878

AC:

AN:

4556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10120

Middle Eastern (MID)

AF:

0.00352

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000699

AC:

AN:

67276

Other (OTH)

AF:

0.0604

AC:

122

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

431

862

1294

1725

2156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0823

Hom.:

904

Bravo

AF:

0.0874

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.0

(source)

DANN

Benign

0.55

PhyloP100

0.065

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over