chr13-109756261-C-T

Position:

• chr13-109756261-C-T

Variant summary

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

The NM_003749.3(IRS2):​c.*43G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,546,828 control chromosomes in the GnomAD database, including 554,526 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 0.84 (54076 hom., cov: 31)
  • Exomes 𝑓: 0.85 (500450 hom.)
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRS2	NM_003749.3	c.*43G>A		3_prime_UTR_variant	2/2	ENST00000375856.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS2	ENST00000375856.5	c.*43G>A		3_prime_UTR_variant	2/2	1	NM_003749.3	P1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128117 AN: 152012 Hom.: 54050 Cov.: 31

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.858

GnomAD3 exomes AF: 0.855 AC: 214608 AN: 251068 Hom.: 91955 AF XY: 0.853 AC XY: 115823 AN XY: 135718

Gnomad AFR exome AF: 0.806

Gnomad AMR exome AF: 0.919

Gnomad ASJ exome AF: 0.883

Gnomad EAS exome AF: 0.784

Gnomad SAS exome AF: 0.833

Gnomad FIN exome AF: 0.865

Gnomad NFE exome AF: 0.855

Gnomad OTH exome AF: 0.861

GnomAD4 exome AF: 0.847 AC: 1180696 AN: 1394698 Hom.: 500450 Cov.: 24 AF XY: 0.846 AC XY: 590729 AN XY: 698004

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.914

Gnomad4 ASJ exome AF: 0.883

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.832

Gnomad4 FIN exome AF: 0.861

Gnomad4 NFE exome AF: 0.847

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.843 AC: 128192 AN: 152130 Hom.: 54076 Cov.: 31 AF XY: 0.843 AC XY: 62689 AN XY: 74368

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.852

Gnomad4 OTH AF: 0.856

Alfa AF: 0.858 Hom.: 49602

Bravo AF: 0.843

Asia WGS AF: 0.811 AC: 2824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.39

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: rs1865434; hg19: chr13-110408608; COSMIC: COSV65476970;