rs7320328

Positions:

• chr13-109755746-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003749.3(IRS2):​c.*558G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 207,278 control chromosomes in the GnomAD database, including 1,685 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 0.077 (1598 hom., cov: 33)
  • Exomes 𝑓: 0.014 (87 hom.)
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRS2	NM_003749.3	c.*558G>T		3_prime_UTR_variant	2/2	ENST00000375856.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRS2	ENST00000375856.5	c.*558G>T		3_prime_UTR_variant	2/2	1	NM_003749.3	P1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11759 AN: 152132 Hom.: 1594 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0143 AC: 787 AN: 55028 Hom.: 87 Cov.: 0 AF XY: 0.0123 AC XY: 317 AN XY: 25818

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.0211

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000869

Gnomad4 OTH exome AF: 0.0246

GnomAD4 genome AF: 0.0774 AC: 11789 AN: 152250 Hom.: 1598 Cov.: 33 AF XY: 0.0733 AC XY: 5454 AN XY: 74438

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.0573

Alfa AF: 0.0186 Hom.: 292

Bravo AF: 0.0872

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.62

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: rs7320328; hg19: chr13-110408093;