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GeneBe

13-109782961-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003749.3(IRS2):c.3093G>A(p.Pro1031=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00945 in 1,426,174 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 6 hom., cov: 33)
Exomes 𝑓: 0.0098 ( 83 hom. )

Consequence

IRS2
NM_003749.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.573
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 Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-109782961-C-T is Benign according to our data. Variant chr13-109782961-C-T is described in ClinVar as [Benign]. Clinvar id is 770424.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.573 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 982 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRS2NM_003749.3 linkuse as main transcriptc.3093G>A p.Pro1031= synonymous_variant 1/2 ENST00000375856.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRS2ENST00000375856.5 linkuse as main transcriptc.3093G>A p.Pro1031= synonymous_variant 1/21 NM_003749.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00648
AC:
982
AN:
151582
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00259
Gnomad AMI
AF:
0.00220
Gnomad AMR
AF:
0.00592
Gnomad ASJ
AF:
0.00404
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00850
Gnomad FIN
AF:
0.00450
Gnomad MID
AF:
0.0160
Gnomad NFE
AF:
0.00986
Gnomad OTH
AF:
0.00337
GnomAD3 exomes
AF:
0.00723
AC:
340
AN:
47038
Hom.:
3
AF XY:
0.00824
AC XY:
219
AN XY:
26578
show subpopulations
Gnomad AFR exome
AF:
0.00242
Gnomad AMR exome
AF:
0.00278
Gnomad ASJ exome
AF:
0.00531
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00839
Gnomad FIN exome
AF:
0.00610
Gnomad NFE exome
AF:
0.0109
Gnomad OTH exome
AF:
0.00800
GnomAD4 exome
AF:
0.00980
AC:
12495
AN:
1274484
Hom.:
83
Cov.:
54
AF XY:
0.00987
AC XY:
6165
AN XY:
624866
show subpopulations
Gnomad4 AFR exome
AF:
0.00181
Gnomad4 AMR exome
AF:
0.00411
Gnomad4 ASJ exome
AF:
0.00258
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00968
Gnomad4 FIN exome
AF:
0.00722
Gnomad4 NFE exome
AF:
0.0106
Gnomad4 OTH exome
AF:
0.0101
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00648
AC:
983
AN:
151690
Hom.:
6
Cov.:
33
AF XY:
0.00608
AC XY:
451
AN XY:
74146
show subpopulations
Gnomad4 AFR
AF:
0.00258
Gnomad4 AMR
AF:
0.00591
Gnomad4 ASJ
AF:
0.00404
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00851
Gnomad4 FIN
AF:
0.00450
Gnomad4 NFE
AF:
0.00986
Gnomad4 OTH
AF:
0.00334
Alfa
AF:
0.00810
Hom.:
1
Bravo
AF:
0.00633
Asia WGS
AF:
0.00443
AC:
15
AN:
3404

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 submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
8.3
Dann
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs374646063; hg19: chr13-110435308; API