rs754204

chr13-109759221-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.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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRS2	NM_003749.3	c.4013-2913G>A		intron_variant		ENST00000375856.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS2	ENST00000375856.5	c.4013-2913G>A		intron_variant		1	NM_003749.3	P1

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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.447

Alfa AF: 0.472 Hom.: 28086

Bravo AF: 0.397

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.57
Dann	Benign	0.57

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: rs754204; hg19: chr13-110411568;