13-109769104-C-T

Variant names:

• chr13-109769104-C-T
• rs9521509
• NM_003749.3:c.4013-12796G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003749.3(IRS2):​c.4013-12796G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,984 control chromosomes in the GnomAD database, including 26,578 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 0.58 (26578 hom., cov: 32)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4013-12796G>A		intron_variant	Intron 1 of 1	ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.4013-12796G>A		intron_variant	Intron 1 of 1	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88083 AN: 151868 Hom.: 26555 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.580 AC: 88150 AN: 151984 Hom.: 26578 Cov.: 32 AF XY: 0.577 AC XY: 42854 AN XY: 74288

African (AFR) AF: 0.750 AC: 31098 AN: 41452

American (AMR) AF: 0.494 AC: 7552 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1796 AN: 5166

South Asian (SAS) AF: 0.525 AC: 2528 AN: 4816

European-Finnish (FIN) AF: 0.567 AC: 5987 AN: 10564

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35392 AN: 67926

Other (OTH) AF: 0.578 AC: 1222 AN: 2114

Alfa AF: 0.535 Hom.: 40448

Bravo AF: 0.582

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.72
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9521509; hg19: chr13-110421451;