Variant 8-40005338-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_194294.5(IDO2):c.679C>A(p.Pro227Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IDO2
NM_194294.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.966

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDO2	NM_194294.5 linkuse as main transcript	c.679C>A	p.Pro227Thr	missense_variant	9/11	ENST00000502986.4
IDO2	NM_001395206.1 linkuse as main transcript	c.679C>A	p.Pro227Thr	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IDO2	ENST00000502986.4 linkuse as main transcript	c.679C>A	p.Pro227Thr	missense_variant	9/11	5	NM_194294.5	P1
IDO2	ENST00000343295.8 linkuse as main transcript	n.2971-8227C>A		intron_variant, non_coding_transcript_variant		2
IDO2	ENST00000418094.1 linkuse as main transcript	n.347-8227C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000833

AC:

AN:

240094

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

130270

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000633

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1426184

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707740

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000468

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

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

Oct 04, 2022

The c.718C>A (p.P240T) alteration is located in exon 9 (coding exon 9) of the IDO2 gene. This alteration results from a C to A substitution at nucleotide position 718, causing the proline (P) at amino acid position 240 to be replaced by a threonine (T). 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

0.17

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.038

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Uncertain

-0.040

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-6.7

D;D

REVEL

Uncertain

0.54

Sift

Benign

0.069

T;T

Sift4G

Benign

0.087

T;T

Vest4

0.76

MutPred

0.89

Gain of catalytic residue at P240 (P = 0.0313);.;

MVP

0.76

MPC

0.077

ClinPred

0.98

GERP RS

5.2

Varity_R

0.41

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.28

Position offset: -11

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