13-109781963-G-A

Position:

• chr13-109781963-G-A

Variant summary

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

The ENST00000375856.5(IRS2):​c.4012+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,508,380 control chromosomes in the GnomAD database, including 25,490 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 0.22 (4408 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21082 hom.)
• Consequence: IRS2 ENST00000375856.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875

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 = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4012+79C>T		intron_variant		ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+79C>T		intron_variant		1	NM_003749.3	ENSP00000365016	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33355 AN: 152026 Hom.: 4401 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0207

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.170 AC: 230565 AN: 1356236 Hom.: 21082 AF XY: 0.170 AC XY: 114490 AN XY: 673144

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.0385

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.219 AC: 33390 AN: 152144 Hom.: 4408 Cov.: 33 AF XY: 0.215 AC XY: 15981 AN XY: 74394

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.179

Alfa AF: 0.177 Hom.: 2475

Bravo AF: 0.225

Asia WGS AF: 0.103 AC: 360 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	0.56
DANN	Benign	0.49

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: rs11618950; hg19: chr13-110434310;