chr13-109782266-C-A
Position:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_003749.3(IRS2):c.3788G>T(p.Gly1263Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000616 in 1,608,982 control chromosomes in the GnomAD database, including 5 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 0.0033 ( 4 hom., cov: 33)
Exomes 𝑓: 0.00034 ( 1 hom. )
Consequence
IRS2
NM_003749.3 missense
NM_003749.3 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 1.07
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0065819025).
BP6
Variant 13-109782266-C-A is Benign according to our data. Variant chr13-109782266-C-A is described in ClinVar as [Benign]. Clinvar id is 785451.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 498 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRS2 | NM_003749.3 | c.3788G>T | p.Gly1263Val | missense_variant | 1/2 | ENST00000375856.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRS2 | ENST00000375856.5 | c.3788G>T | p.Gly1263Val | missense_variant | 1/2 | 1 | NM_003749.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00328 AC: 497AN: 151538Hom.: 4 Cov.: 33
GnomAD3 genomes
AF:
AC:
497
AN:
151538
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000780 AC: 181AN: 232038Hom.: 2 AF XY: 0.000614 AC XY: 79AN XY: 128678
GnomAD3 exomes
AF:
AC:
181
AN:
232038
Hom.:
AF XY:
AC XY:
79
AN XY:
128678
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000338 AC: 493AN: 1457330Hom.: 1 Cov.: 33 AF XY: 0.000292 AC XY: 212AN XY: 724892
GnomAD4 exome
AF:
AC:
493
AN:
1457330
Hom.:
Cov.:
33
AF XY:
AC XY:
212
AN XY:
724892
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00328 AC: 498AN: 151652Hom.: 4 Cov.: 33 AF XY: 0.00313 AC XY: 232AN XY: 74110
GnomAD4 genome
AF:
AC:
498
AN:
151652
Hom.:
Cov.:
33
AF XY:
AC XY:
232
AN XY:
74110
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
38
ESP6500EA
AF:
AC:
2
ExAC
AF:
AC:
115
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at