NM_003749.3:c.*68A>G

Variant names:

• chr13-109756236-T-C
• rs74123739
• NM_003749.3:c.*68A>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.*68A>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 0.00514 in 1,346,236 control chromosomes in the GnomAD database, including 276 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 0.025 (143 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (133 hom.)
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003749.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS2	NM_003749.3	MANE Select	c.*68A>G		3_prime_UTR	Exon 2 of 2	NP_003740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRS2	ENST00000375856.5	TSL:1 MANE Select	c.*68A>G		3_prime_UTR	Exon 2 of 2	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3829 AN: 152186 Hom.: 143 Cov.: 33

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.00258 AC: 3083 AN: 1193932 Hom.: 133 Cov.: 17 AF XY: 0.00216 AC XY: 1313 AN XY: 607672

African (AFR) AF: 0.0900 AC: 2534 AN: 28146

American (AMR) AF: 0.00390 AC: 173 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24398

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38474

South Asian (SAS) AF: 0.000123 AC: 10 AN: 80996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00264 AC: 14 AN: 5308

European-Non Finnish (NFE) AF: 0.000127 AC: 110 AN: 867370

Other (OTH) AF: 0.00466 AC: 241 AN: 51760

GnomAD4 genome AF: 0.0252 AC: 3838 AN: 152304 Hom.: 143 Cov.: 33 AF XY: 0.0244 AC XY: 1820 AN XY: 74476

African (AFR) AF: 0.0887 AC: 3684 AN: 41548

American (AMR) AF: 0.00679 AC: 104 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68032

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.0133 Hom.: 24

Bravo AF: 0.0278

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.086
DANN	Benign	0.59
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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: rs74123739; hg19: chr13-110408583;