rs9559648

chr13-109771448-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+10594G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,982 control chromosomes in the GnomAD database, including 7,673 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 0.32 (7673 hom., cov: 33)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRS2	NM_003749.3	c.4012+10594G>A		intron_variant		ENST00000375856.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+10594G>A		intron_variant		1	NM_003749.3	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47877 AN: 151864 Hom.: 7671 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.315 AC: 47901 AN: 151982 Hom.: 7673 Cov.: 33 AF XY: 0.314 AC XY: 23317 AN XY: 74270

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.354

Alfa AF: 0.225 Hom.: 978

Bravo AF: 0.310

Asia WGS AF: 0.304 AC: 1052 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.042
Dann	Benign	0.18

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: rs9559648; hg19: chr13-110423795;