rs3742210

Variant names:

• chr13-109783885-G-A
• rs3742210
• NM_003749.3:c.2169C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-109783885-G-A
• chr13-109783885-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003749.3(IRS2):​c.2169C>T​(p.Ser723Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,548,092 control chromosomes in the GnomAD database, including 263,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (26532 hom., cov: 33)
  • Exomes 𝑓: 0.58 (236747 hom.)
• Consequence: IRS2 NM_003749.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.01

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-109783885-G-A is Benign according to our data. Variant chr13-109783885-G-A is described in ClinVar as [Benign]. Clinvar id is 3060213.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.2169C>T	p.Ser723Ser	synonymous_variant	Exon 1 of 2	ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.2169C>T	p.Ser723Ser	synonymous_variant	Exon 1 of 2	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89319 AN: 151768 Hom.: 26502 Cov.: 33

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.557

GnomAD3 exomes AF: 0.584 AC: 82284 AN: 140836 Hom.: 24376 AF XY: 0.576 AC XY: 43806 AN XY: 75992

Gnomad AFR exome AF: 0.589

Gnomad AMR exome AF: 0.692

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.467

Gnomad SAS exome AF: 0.493

Gnomad FIN exome AF: 0.604

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.569

GnomAD4 exome AF: 0.581 AC: 810568 AN: 1396214 Hom.: 236747 Cov.: 93 AF XY: 0.578 AC XY: 398444 AN XY: 688832

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.685

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.589 AC: 89395 AN: 151878 Hom.: 26532 Cov.: 33 AF XY: 0.589 AC XY: 43686 AN XY: 74200

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.554

Alfa AF: 0.556 Hom.: 5032

Bravo AF: 0.594

Asia WGS AF: 0.471 AC: 1631 AN: 3454

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

IRS2-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.78
CADD	Benign	0.36
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs3742210; hg19: chr13-110436232; COSMIC: COSV65479217; COSMIC: COSV65479217;