NM_003749.3:c.4013-2913G>A

Variant names:

• chr13-109759221-C-T
• rs754204
• NM_003749.3:c.4013-2913G>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.4013-2913G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,040 control chromosomes in the GnomAD database, including 14,042 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 0.42 (14042 hom., cov: 31)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003749.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS2	NM_003749.3	MANE Select	c.4013-2913G>A		intron	N/A	NP_003740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS2	ENST00000375856.5	TSL:1 MANE Select	c.4013-2913G>A		intron	N/A	ENSP00000365016.3	Q9Y4H2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63098 AN: 151922 Hom.: 14048 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.415 AC: 63105 AN: 152040 Hom.: 14042 Cov.: 31 AF XY: 0.419 AC XY: 31107 AN XY: 74326

African (AFR) AF: 0.251 AC: 10401 AN: 41464

American (AMR) AF: 0.423 AC: 6464 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1637 AN: 5146

South Asian (SAS) AF: 0.460 AC: 2214 AN: 4814

European-Finnish (FIN) AF: 0.569 AC: 6018 AN: 10576

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33222 AN: 67970

Other (OTH) AF: 0.447 AC: 946 AN: 2114

Alfa AF: 0.459 Hom.: 61606

Bravo AF: 0.397

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.57
PhyloP100		-1.4
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: rs754204; hg19: chr13-110411568;