13-109762666-T-C

Variant names:

• chr13-109762666-T-C
• rs7987237
• NM_003749.3:c.4013-6358A>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.4013-6358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,100 control chromosomes in the GnomAD database, including 56,333 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 0.86 (56333 hom., cov: 31)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885
• Publications: 6 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.887 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.4013-6358A>G		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.4013-6358A>G		intron	N/A	ENSP00000365016.3	Q9Y4H2

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130779 AN: 151980 Hom.: 56294 Cov.: 31

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.876

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

GnomAD4 genome AF: 0.860 AC: 130873 AN: 152100 Hom.: 56333 Cov.: 31 AF XY: 0.860 AC XY: 63976 AN XY: 74352

African (AFR) AF: 0.868 AC: 35984 AN: 41480

American (AMR) AF: 0.900 AC: 13764 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3091 AN: 3472

East Asian (EAS) AF: 0.776 AC: 3981 AN: 5132

South Asian (SAS) AF: 0.828 AC: 3992 AN: 4822

European-Finnish (FIN) AF: 0.860 AC: 9105 AN: 10588

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58078 AN: 68002

Other (OTH) AF: 0.873 AC: 1836 AN: 2104

Alfa AF: 0.866 Hom.: 10489

Bravo AF: 0.864

Asia WGS AF: 0.814 AC: 2833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.45
PhyloP100		-0.89
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: rs7987237; hg19: chr13-110415013;