13-109755559-T-C

Position:

• chr13-109755559-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.*745A>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 0.286 in 206,506 control chromosomes in the GnomAD database, including 9,622 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 0.27 (6493 hom., cov: 32)
  • Exomes 𝑓: 0.33 (3129 hom.)
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS2	NM_003749.3	c.*745A>G		3_prime_UTR_variant	2/2	ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856	c.*745A>G		3_prime_UTR_variant	2/2	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41250 AN: 152014 Hom.: 6493 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.329 AC: 17875 AN: 54372 Hom.: 3129 Cov.: 0 AF XY: 0.326 AC XY: 8243 AN XY: 25254

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.271 AC: 41263 AN: 152134 Hom.: 6493 Cov.: 32 AF XY: 0.274 AC XY: 20348 AN XY: 74368

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.267

Alfa AF: 0.222 Hom.: 811

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.3
DANN	Benign	0.50

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: rs2289046; hg19: chr13-110407906;