Variant 8-39989811-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_194294.5(IDO2):c.640A>C(p.Ile214Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,600,758 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 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

IDO2
NM_194294.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09283367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDO2	NM_194294.5 linkuse as main transcript	c.640A>C	p.Ile214Leu	missense_variant	8/11	ENST00000502986.4
IDO2	NM_001395206.1 linkuse as main transcript	c.640A>C	p.Ile214Leu	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IDO2	ENST00000502986.4 linkuse as main transcript	c.640A>C	p.Ile214Leu	missense_variant	8/11	5	NM_194294.5	P1
	ENST00000517623.1 linkuse as main transcript	n.135-2313T>G		intron_variant, non_coding_transcript_variant		4
IDO2	ENST00000343295.8 linkuse as main transcript	n.2943A>C		non_coding_transcript_exon_variant	9/11	2
IDO2	ENST00000418094.1 linkuse as main transcript	n.319A>C		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000706

AC:

AN:

226634

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

122162

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000246

Gnomad NFE exome

AF:

0.0000980

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.0000497

AC:

AN:

1448568

Hom.:

Cov.:

AF XY:

0.0000542

AC XY:

AN XY:

719140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000133

Gnomad4 NFE exome

AF:

0.0000561

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000160

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000828

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 14, 2023

The c.679A>C (p.I227L) alteration is located in exon 8 (coding exon 8) of the IDO2 gene. This alteration results from a A to C substitution at nucleotide position 679, causing the isoleucine (I) at amino acid position 227 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Benign

0.81

DEOGEN2

Benign

0.0036

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.044

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.85

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.080

Sift

Benign

1.0

T;T

Sift4G

Benign

0.33

T;T

Vest4

0.36

MutPred

0.59

Loss of MoRF binding (P = 0.1977);.;

MVP

0.15

MPC

0.013

ClinPred

0.066

GERP RS

5.7

Varity_R

0.17

gMVP

0.26

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