rs1034104

Positions:

• chr13-109752780-G-C
• chr13-109752780-G-T

Variant summary

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

The NM_003749.3(IRS2):​c.*3524C>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 0.754 in 152,068 control chromosomes in the GnomAD database, including 44,722 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 0.75 (44722 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS2	NM_003749.3	c.*3524C>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	ENST00000375856.5	c.*3524C>G		3_prime_UTR_variant	2/2	1	NM_003749.3	ENSP00000365016	P1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114573 AN: 151952 Hom.: 44712 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.792

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.754 AC: 114621 AN: 152068 Hom.: 44722 Cov.: 32 AF XY: 0.758 AC XY: 56335 AN XY: 74334

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.791

Alfa AF: 0.750 Hom.: 2506

Bravo AF: 0.745

Asia WGS AF: 0.769 AC: 2675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.44

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: rs1034104; hg19: chr13-110405127;