chr13-109770044-C-T

Position:

• chr13-109770044-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.4012+11998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,272 control chromosomes in the GnomAD database, including 254 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 0.044 (254 hom., cov: 33)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4012+11998G>A		intron_variant		ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+11998G>A		intron_variant		1	NM_003749.3	ENSP00000365016	P1

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6740 AN: 152154 Hom.: 254 Cov.: 33

Gnomad AFR AF: 0.00989

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00972

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0443 AC: 6739 AN: 152272 Hom.: 254 Cov.: 33 AF XY: 0.0465 AC XY: 3463 AN XY: 74458

Gnomad4 AFR AF: 0.00986

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00931

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0617

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0549 Hom.: 145

Bravo AF: 0.0330

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.53

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: rs9515120; hg19: chr13-110422391;