Variant 8-39987935-G-T 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.514G>T(p.Ala172Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000689 in 1,610,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

IDO2
NM_194294.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.699

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=0.028235316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDO2	NM_194294.5 linkuse as main transcript	c.514G>T	p.Ala172Ser	missense_variant	7/11	ENST00000502986.4	NP_919270.3	Q6ZQW0
IDO2	NM_001395206.1 linkuse as main transcript	c.514G>T	p.Ala172Ser	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.514G>T	p.Ala172Ser	missense_variant	7/11	5	NM_194294.5	ENSP00000443432.2	Q6ZQW0
IDO2	ENST00000343295.8 linkuse as main transcript	n.2817G>T		non_coding_transcript_exon_variant	8/11	2
IDO2	ENST00000418094.1 linkuse as main transcript	n.193G>T		non_coding_transcript_exon_variant	1/4	2
ENSG00000253939	ENST00000517623.1 linkuse as main transcript	n.135-437C>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000155

AC:

AN:

245522

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

132992

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00314

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000538

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000699

AC:

102

AN:

1458834

Hom.:

Cov.:

AF XY:

0.0000731

AC XY:

AN XY:

725416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00289

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000911

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

Dec 27, 2022

The c.553G>T (p.A185S) alteration is located in exon 7 (coding exon 7) of the IDO2 gene. This alteration results from a G to T substitution at nucleotide position 553, causing the alanine (A) at amino acid position 185 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.081

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.039

D;D

Vest4

0.32

MVP

0.22

MPC

0.013

ClinPred

0.080

GERP RS

3.8

Varity_R

0.19

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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