rs7999797

chr13-109773653-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	UniProt
IRS2	NM_003749.3	c.4012+8389C>T		intron_variant		ENST00000375856.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS2	ENST00000375856.5	c.4012+8389C>T		intron_variant		1	NM_003749.3	P1

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

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.605

Alfa AF: 0.553 Hom.: 31075

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

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: rs7999797; hg19: chr13-110426000;