chr13-109755559-T-C

Variant names:

• chr13-109755559-T-C
• rs2289046
• NM_003749.3:c.*745A>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.*745A>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 0.286 in 206,506 control chromosomes in the GnomAD database, including 9,622 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 0.27 (6493 hom., cov: 32)
  • Exomes 𝑓: 0.33 (3129 hom.)
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 34 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRS2	NM_003749.3	c.*745A>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.*745A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41250 AN: 152014 Hom.: 6493 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.329 AC: 17875 AN: 54372 Hom.: 3129 Cov.: 0 AF XY: 0.326 AC XY: 8243 AN XY: 25254

African (AFR) AF: 0.122 AC: 301 AN: 2472

American (AMR) AF: 0.401 AC: 619 AN: 1542

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1123 AN: 3478

East Asian (EAS) AF: 0.454 AC: 3843 AN: 8468

South Asian (SAS) AF: 0.335 AC: 154 AN: 460

European-Finnish (FIN) AF: 0.184 AC: 7 AN: 38

Middle Eastern (MID) AF: 0.283 AC: 95 AN: 336

European-Non Finnish (NFE) AF: 0.312 AC: 10270 AN: 32952

Other (OTH) AF: 0.316 AC: 1463 AN: 4626

GnomAD4 genome AF: 0.271 AC: 41263 AN: 152134 Hom.: 6493 Cov.: 32 AF XY: 0.274 AC XY: 20348 AN XY: 74368

African (AFR) AF: 0.114 AC: 4748 AN: 41532

American (AMR) AF: 0.385 AC: 5885 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3466

East Asian (EAS) AF: 0.457 AC: 2362 AN: 5166

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4820

European-Finnish (FIN) AF: 0.262 AC: 2775 AN: 10576

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22023 AN: 67986

Other (OTH) AF: 0.267 AC: 564 AN: 2110

Alfa AF: 0.219 Hom.: 815

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.3
DANN	Benign	0.50
PhyloP100		0.28
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: rs2289046; hg19: chr13-110407906;