rs9587979

Variant names:

• chr13-109752894-G-A
• rs9587979
• NM_003749.3:c.*3410C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003749.3(IRS2):​c.*3410C>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 0.0497 in 150,692 control chromosomes in the GnomAD database, including 651 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 0.050 (651 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IRS2 NM_003749.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544
• 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=-0.83).
• 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.*3410C>T		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.*3410C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_003749.3	ENSP00000365016.3

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7464 AN: 150592 Hom.: 649 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000630

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000325

Gnomad OTH AF: 0.0376

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0497 AC: 7482 AN: 150692 Hom.: 651 Cov.: 32 AF XY: 0.0474 AC XY: 3485 AN XY: 73516

African (AFR) AF: 0.174 AC: 7136 AN: 40976

American (AMR) AF: 0.0160 AC: 243 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.000631 AC: 3 AN: 4752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000325 AC: 22 AN: 67728

Other (OTH) AF: 0.0372 AC: 78 AN: 2094

Alfa AF: 0.0201 Hom.: 633

Bravo AF: 0.0556

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.30
PhyloP100		0.54

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: rs9587979; hg19: chr13-110405241;