rs2241745

chr13-109770184-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+11858G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,236 control chromosomes in the GnomAD database, including 58,105 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 0.87 (58105 hom., cov: 32)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRS2	NM_003749.3	c.4012+11858G>A		intron_variant		ENST00000375856.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+11858G>A		intron_variant		1	NM_003749.3	P1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132820 AN: 152118 Hom.: 58058 Cov.: 32

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.885

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

GnomAD4 genome AF: 0.873 AC: 132922 AN: 152236 Hom.: 58105 Cov.: 32 AF XY: 0.873 AC XY: 64959 AN XY: 74414

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.882

Alfa AF: 0.864 Hom.: 21997

Bravo AF: 0.879

Asia WGS AF: 0.812 AC: 2828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.30
Dann	Benign	0.62

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: rs2241745; hg19: chr13-110422531;