rs7981170

Positions:

• chr13-109779227-C-T

Variant summary

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

The NM_003749.3(IRS2):​c.4012+2815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,152 control chromosomes in the GnomAD database, including 4,432 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 0.22 (4432 hom., cov: 33)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRS2	NM_003749.3	c.4012+2815G>A		intron_variant		ENST00000375856.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+2815G>A		intron_variant		1	NM_003749.3	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32799 AN: 152034 Hom.: 4424 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.216 AC: 32840 AN: 152152 Hom.: 4432 Cov.: 33 AF XY: 0.212 AC XY: 15746 AN XY: 74382

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0303

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.181

Alfa AF: 0.167 Hom.: 3057

Bravo AF: 0.224

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.1
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7981170; hg19: chr13-110431574;