Variant chr8-40005374-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_194294.5(IDO2):c.715T>A(p.Ser239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,561,968 control chromosomes in the GnomAD database, including 892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 69 hom., cov: 33)

Exomes 𝑓: 0.031 ( 823 hom. )

Consequence

IDO2
NM_194294.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.45

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015613109).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0238 (3620/152348) while in subpopulation NFE AF= 0.0375 (2549/68034). AF 95% confidence interval is 0.0363. There are 69 homozygotes in gnomad4. There are 1715 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDO2	NM_194294.5 link	c.715T>A	p.Ser239Thr	missense_variant	9/11	ENST00000502986.4	NP_919270.3	Q6ZQW0
IDO2	NM_001395206.1 link	c.715T>A	p.Ser239Thr	missense_variant	8/10		NP_001382135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IDO2	ENST00000502986.4 link	c.715T>A	p.Ser239Thr	missense_variant	9/11	5	NM_194294.5	ENSP00000443432.2	Q6ZQW0
IDO2	ENST00000343295.8 link	n.2971-8191T>A		intron_variant		2
IDO2	ENST00000418094.1 link	n.347-8191T>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3620

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0375

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0203

AC:

4824

AN:

238208

Hom.:

AF XY:

0.0203

AC XY:

2627

AN XY:

129262

show subpopulations

Gnomad AFR exome

AF:

0.00509

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00539

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0310

AC:

43720

AN:

1409620

Hom.:

823

Cov.:

AF XY:

0.0306

AC XY:

21365

AN XY:

699254

show subpopulations

Gnomad4 AFR exome

AF:

0.00489

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.00650

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00472

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.0366

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0238

AC:

3620

AN:

152348

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1715

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00642

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.00664

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.0370

Gnomad4 NFE

AF:

0.0375

Gnomad4 OTH

AF:

0.0217

Alfa

AF:

0.0322

Hom.:

Bravo

AF:

0.0213

TwinsUK

AF:

0.0356

AC:

132

ALSPAC

AF:

0.0392

AC:

151

ESP6500AA

AF:

0.00614

AC:

ESP6500EA

AF:

0.0309

AC:

254

ExAC

AF:

0.0220

AC:

2658

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.83

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.012

D;D

Vest4

0.20

MPC

0.026

ClinPred

0.046

GERP RS

3.6

Varity_R

0.46

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over