rs1044364

Variant names:

• chr13-109755299-T-C
• rs1044364
• NM_003749.3:c.*1005A>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.*1005A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 227,974 control chromosomes in the GnomAD database, including 1,006 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 0.088 (847 hom., cov: 30)
  • Exomes 𝑓: 0.051 (159 hom.)
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.*1005A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000375856.5	NP_003740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRS2	ENST00000375856.5	c.*1005A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13356 AN: 151426 Hom.: 833 Cov.: 30

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.0351

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0825

GnomAD4 exome AF: 0.0514 AC: 3927 AN: 76442 Hom.: 159 Cov.: 0 AF XY: 0.0498 AC XY: 1761 AN XY: 35328

African (AFR) AF: 0.166 AC: 592 AN: 3570

American (AMR) AF: 0.0877 AC: 203 AN: 2316

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 61 AN: 4872

East Asian (EAS) AF: 0.0335 AC: 364 AN: 10878

South Asian (SAS) AF: 0.0258 AC: 17 AN: 658

European-Finnish (FIN) AF: 0.0556 AC: 3 AN: 54

Middle Eastern (MID) AF: 0.0711 AC: 34 AN: 478

European-Non Finnish (NFE) AF: 0.0474 AC: 2237 AN: 47210

Other (OTH) AF: 0.0649 AC: 416 AN: 6406

GnomAD4 genome AF: 0.0885 AC: 13409 AN: 151532 Hom.: 847 Cov.: 30 AF XY: 0.0877 AC XY: 6493 AN XY: 74060

African (AFR) AF: 0.174 AC: 7186 AN: 41208

American (AMR) AF: 0.0819 AC: 1246 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.0387 AC: 200 AN: 5162

South Asian (SAS) AF: 0.0351 AC: 169 AN: 4816

European-Finnish (FIN) AF: 0.0505 AC: 527 AN: 10430

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0551 AC: 3745 AN: 67942

Other (OTH) AF: 0.0817 AC: 171 AN: 2094

Alfa AF: 0.0645 Hom.: 307

Bravo AF: 0.0982

Asia WGS AF: 0.0500 AC: 175 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	0.87
DANN	Benign	0.46
PhyloP100		-0.092
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: rs1044364; hg19: chr13-110407646;