Variant 8-39987884-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_194294.5(IDO2):c.463A>G(p.Ile155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000771 in 1,607,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 0 hom. )

Consequence

IDO2
NM_194294.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

IDO2 (HGNC:27269): (indoleamine 2,3-dioxygenase 2) Along with the enzymes encoded by the INDO (MIM 147435) and TDO2 (MIM 191070) genes, the enzyme encoded by the INDOL1 gene metabolizes tryptophan in the kynurenine pathway (Ball et al., 2007 [PubMed 17499941]).[supplied by OMIM, Feb 2011]

IDO2 links:

IDO2 (HGNC:):

IDO2 links:

Genome browser will be placed here

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=0.054882884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDO2	NM_194294.5 linkuse as main transcript	c.463A>G	p.Ile155Val	missense_variant	7/11	ENST00000502986.4	NP_919270.3	Q6ZQW0
IDO2	NM_001395206.1 linkuse as main transcript	c.463A>G	p.Ile155Val	missense_variant	6/10		NP_001382135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IDO2	ENST00000502986.4 linkuse as main transcript	c.463A>G	p.Ile155Val	missense_variant	7/11	5	NM_194294.5	ENSP00000443432.2	Q6ZQW0
IDO2	ENST00000343295.8 linkuse as main transcript	n.2766A>G		non_coding_transcript_exon_variant	8/11	2
IDO2	ENST00000418094.1 linkuse as main transcript	n.142A>G		non_coding_transcript_exon_variant	1/4	2
ENSG00000253939	ENST00000517623.1 linkuse as main transcript	n.135-386T>C		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000464

AC:

113

AN:

243654

Hom.:

AF XY:

0.000409

AC XY:

AN XY:

131874

show subpopulations

Gnomad AFR exome

AF:

0.0000676

Gnomad AMR exome

AF:

0.000472

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000343

Gnomad FIN exome

AF:

0.0000936

Gnomad NFE exome

AF:

0.000839

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000808

AC:

1176

AN:

1455170

Hom.:

Cov.:

AF XY:

0.000791

AC XY:

572

AN XY:

723572

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.000996

Gnomad4 OTH exome

AF:

0.000648

GnomAD4 genome

AF:

0.000414

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000674

Hom.:

Bravo

AF:

0.000404

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.000606

AC:

ExAC

AF:

0.000397

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

The c.502A>G (p.I168V) alteration is located in exon 7 (coding exon 7) of the IDO2 gene. This alteration results from a A to G substitution at nucleotide position 502, causing the isoleucine (I) at amino acid position 168 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0091

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.087

Sift

Benign

0.068

T;T

Sift4G

Benign

0.22

T;T

Vest4

0.38

MVP

0.19

MPC

0.016

ClinPred

0.030

GERP RS

4.5

Varity_R

0.082

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over