chr13-109782884-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_003749.3(IRS2):c.3170G>A(p.Gly1057Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,562,240 control chromosomes in the GnomAD database, including 86,943 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.29 ( 7081 hom., cov: 32)
Exomes 𝑓: 0.33 ( 79862 hom. )
Consequence
IRS2
NM_003749.3 missense
NM_003749.3 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 0.425
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=3.8087368E-4).
BP6
?
Variant 13-109782884-C-T is Benign according to our data. Variant chr13-109782884-C-T is described in ClinVar as [Benign]. Clinvar id is 8820.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRS2 | NM_003749.3 | c.3170G>A | p.Gly1057Asp | missense_variant | 1/2 | ENST00000375856.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRS2 | ENST00000375856.5 | c.3170G>A | p.Gly1057Asp | missense_variant | 1/2 | 1 | NM_003749.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.287 AC: 43522AN: 151442Hom.: 7078 Cov.: 32
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?
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GnomAD3 exomes AF: 0.350 AC: 54931AN: 156960Hom.: 10029 AF XY: 0.345 AC XY: 29439AN XY: 85284
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GnomAD4 exome AF: 0.332 AC: 469031AN: 1410682Hom.: 79862 Cov.: 54 AF XY: 0.331 AC XY: 230790AN XY: 696988
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GnomAD4 genome ? AF: 0.287 AC: 43535AN: 151558Hom.: 7081 Cov.: 32 AF XY: 0.291 AC XY: 21534AN XY: 74054
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1292
ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
IRS2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
DIABETES, TYPE II, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Oct 01, 2001 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
P
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at