chr13-109755468-C-A

Position:

• chr13-109755468-C-A

Variant summary

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

The NM_003749.3(IRS2):​c.*836G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 217,118 control chromosomes in the GnomAD database, including 10,240 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 (6484 hom., cov: 32)
  • Exomes 𝑓: 0.33 (3756 hom.)
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499

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=-0.72).
• 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.*836G>T		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	ENST00000375856.5	c.*836G>T		3_prime_UTR_variant	2/2	1	NM_003749.3	ENSP00000365016	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41208 AN: 151832 Hom.: 6484 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.332 AC: 21663 AN: 65168 Hom.: 3756 Cov.: 0 AF XY: 0.330 AC XY: 9953 AN XY: 30172

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.271 AC: 41221 AN: 151950 Hom.: 6484 Cov.: 32 AF XY: 0.274 AC XY: 20333 AN XY: 74272

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.268

Alfa AF: 0.297 Hom.: 3035

Bravo AF: 0.275

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.7
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2289047; hg19: chr13-110407815;