chr13-109779544-C-T

Variant names:

• chr13-109779544-C-T
• rs7981705
• NM_003749.3:c.4012+2498G>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.4012+2498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,078 control chromosomes in the GnomAD database, including 3,935 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 0.21 (3935 hom., cov: 33)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 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.4012+2498G>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.4012+2498G>A		intron	N/A	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31449 AN: 151960 Hom.: 3928 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.207 AC: 31481 AN: 152078 Hom.: 3935 Cov.: 33 AF XY: 0.203 AC XY: 15126 AN XY: 74370

African (AFR) AF: 0.356 AC: 14730 AN: 41428

American (AMR) AF: 0.172 AC: 2624 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3468

East Asian (EAS) AF: 0.0301 AC: 156 AN: 5182

South Asian (SAS) AF: 0.127 AC: 614 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1603 AN: 10592

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10606 AN: 67992

Other (OTH) AF: 0.175 AC: 369 AN: 2112

Alfa AF: 0.151 Hom.: 1141

Bravo AF: 0.214

Asia WGS AF: 0.103 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.53
PhyloP100		-0.56
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: rs7981705; hg19: chr13-110431891;