rs913949

Positions:

• chr13-109759449-G-A
• chr13-109759449-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003749.3(IRS2):​c.4013-3141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,024 control chromosomes in the GnomAD database, including 38,102 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 0.68 (38102 hom., cov: 31)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4013-3141C>T		intron_variant		ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.4013-3141C>T		intron_variant		1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103166 AN: 151904 Hom.: 38110 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.720

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.679 AC: 103175 AN: 152024 Hom.: 38102 Cov.: 31 AF XY: 0.684 AC XY: 50798 AN XY: 74310

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.719

Alfa AF: 0.794 Hom.: 79768

Bravo AF: 0.662

Asia WGS AF: 0.725 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.68

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: rs913949; hg19: chr13-110411796;