13-109756989-A-C

Variant names:

• chr13-109756989-A-C
• rs9515119
• NM_003749.3:c.4013-681T>G

Variant summary

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

The NM_003749.3(IRS2):​c.4013-681T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,040 control chromosomes in the GnomAD database, including 6,487 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 (6487 hom., cov: 32)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 11 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 (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4013-681T>G		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.4013-681T>G		intron_variant	Intron 1 of 1	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41229 AN: 151922 Hom.: 6487 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.271 AC: 41241 AN: 152040 Hom.: 6487 Cov.: 32 AF XY: 0.274 AC XY: 20345 AN XY: 74324

African (AFR) AF: 0.115 AC: 4756 AN: 41502

American (AMR) AF: 0.385 AC: 5876 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1125 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2355 AN: 5144

South Asian (SAS) AF: 0.304 AC: 1461 AN: 4810

European-Finnish (FIN) AF: 0.263 AC: 2778 AN: 10578

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22005 AN: 67960

Other (OTH) AF: 0.267 AC: 562 AN: 2108

Alfa AF: 0.308 Hom.: 23634

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.011
DANN	Benign	0.49
PhyloP100		-2.5
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: rs9515119; hg19: chr13-110409336;