rs7999797

Variant names:

• chr13-109773653-G-A
• rs7999797
• NM_003749.3:c.4012+8389C>T

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+8389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,096 control chromosomes in the GnomAD database, including 29,320 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 0.61 (29320 hom., cov: 33)
• Consequence: IRS2 NM_003749.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.4012+8389C>T		intron_variant	Intron 1 of 1	ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+8389C>T		intron_variant	Intron 1 of 1	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92373 AN: 151978 Hom.: 29301 Cov.: 33

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.608 AC: 92438 AN: 152096 Hom.: 29320 Cov.: 33 AF XY: 0.603 AC XY: 44817 AN XY: 74334

African (AFR) AF: 0.796 AC: 33027 AN: 41484

American (AMR) AF: 0.521 AC: 7973 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1858 AN: 3464

East Asian (EAS) AF: 0.328 AC: 1693 AN: 5166

South Asian (SAS) AF: 0.544 AC: 2626 AN: 4830

European-Finnish (FIN) AF: 0.570 AC: 6022 AN: 10562

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37246 AN: 67980

Other (OTH) AF: 0.605 AC: 1278 AN: 2112

Alfa AF: 0.561 Hom.: 40875

Bravo AF: 0.611

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.79
DANN	Benign	0.59
PhyloP100		-0.37
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: rs7999797; hg19: chr13-110426000;