rs1044364

Positions:

• chr13-109755299-T-C

Variant summary

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

The NM_003749.3(IRS2):​c.*1005A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 227,974 control chromosomes in the GnomAD database, including 1,006 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 0.088 (847 hom., cov: 30)
  • Exomes 𝑓: 0.051 (159 hom.)
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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 (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRS2	NM_003749.3	c.*1005A>G		3_prime_UTR_variant	2/2	ENST00000375856.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS2	ENST00000375856.5	c.*1005A>G		3_prime_UTR_variant	2/2	1	NM_003749.3	P1

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13356 AN: 151426 Hom.: 833 Cov.: 30

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.0351

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0825

GnomAD4 exome AF: 0.0514 AC: 3927 AN: 76442 Hom.: 159 Cov.: 0 AF XY: 0.0498 AC XY: 1761 AN XY: 35328

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.0335

Gnomad4 SAS exome AF: 0.0258

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0649

GnomAD4 genome AF: 0.0885 AC: 13409 AN: 151532 Hom.: 847 Cov.: 30 AF XY: 0.0877 AC XY: 6493 AN XY: 74060

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.0351

Gnomad4 FIN AF: 0.0505

Gnomad4 NFE AF: 0.0551

Gnomad4 OTH AF: 0.0817

Alfa AF: 0.0667 Hom.: 222

Bravo AF: 0.0982

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.87
DANN	Benign	0.46

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: rs1044364; hg19: chr13-110407646;