rs1805097

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003749.3(IRS2):ā€‹c.3170G>Cā€‹(p.Gly1057Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IRS2
NM_003749.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.425
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059045613).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IRS2NM_003749.3 linkc.3170G>C p.Gly1057Ala missense_variant Exon 1 of 2 ENST00000375856.5 NP_003740.2 Q9Y4H2Q9P084

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IRS2ENST00000375856.5 linkc.3170G>C p.Gly1057Ala missense_variant Exon 1 of 2 1 NM_003749.3 ENSP00000365016.3 Q9Y4H2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1410840
Hom.:
0
Cov.:
54
AF XY:
0.00
AC XY:
0
AN XY:
697078
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
8.9
DANN
Benign
0.15
DEOGEN2
Benign
0.27
T
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.91
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
0.25
N
REVEL
Benign
0.038
Sift
Benign
0.64
T
Sift4G
Benign
0.94
T
Polyphen
0.0020
B
Vest4
0.16
MutPred
0.15
Gain of phosphorylation at T1052 (P = 0.1455);
MVP
0.45
ClinPred
0.018
T
GERP RS
2.1
Varity_R
0.035
gMVP
0.30

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1805097; hg19: chr13-110435231; API