dbSNP rs10109853: IDO2:p.Arg235Trp (chr8-40005362-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_194294.5(IDO2):c.703C>T(p.Arg235Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,553,334 control chromosomes in the GnomAD database, including 195,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16804 hom., cov: 33)

Exomes 𝑓: 0.50 ( 179000 hom. )

Consequence

IDO2
NM_194294.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.34

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 -16 ACMG points.

BP6

Variant 8-40005362-C-T is Benign according to our data. Variant chr8-40005362-C-T is described in ClinVar as [Benign]. Clinvar id is 1275323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDO2	NM_194294.5 link	c.703C>T	p.Arg235Trp	missense_variant	Exon 9 of 11	ENST00000502986.4	NP_919270.3	Q6ZQW0
IDO2	NM_001395206.1 link	c.703C>T	p.Arg235Trp	missense_variant	Exon 8 of 10		NP_001382135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IDO2	ENST00000502986.4 link	c.703C>T	p.Arg235Trp	missense_variant	Exon 9 of 11	5	NM_194294.5	ENSP00000443432.2	Q6ZQW0
IDO2	ENST00000343295.8 link	n.2971-8203C>T		intron_variant	Intron 9 of 10	2
IDO2	ENST00000418094.1 link	n.347-8203C>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70106

AN:

151900

Hom.:

16793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.358

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.529

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.513

Gnomad OTH

AF:

0.448

GnomAD3 exomes

AF:

0.481

AC:

111843

AN:

232302

Hom.:

28302

AF XY:

0.484

AC XY:

60867

AN XY:

125824

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.233

Gnomad SAS exome

AF:

0.535

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.496

Gnomad OTH exome

AF:

0.490

GnomAD4 exome

AF:

0.500

AC:

701099

AN:

1401316

Hom.:

179000

Cov.:

AF XY:

0.501

AC XY:

347603

AN XY:

694110

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.528

Gnomad4 EAS exome

AF:

0.264

Gnomad4 SAS exome

AF:

0.528

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.509

Gnomad4 OTH exome

AF:

0.480

GnomAD4 genome

AF:

0.461

AC:

70139

AN:

152018

Hom.:

16804

Cov.:

AF XY:

0.463

AC XY:

34422

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.465

Gnomad4 ASJ

AF:

0.529

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.544

Gnomad4 FIN

AF:

0.582

Gnomad4 NFE

AF:

0.513

Gnomad4 OTH

AF:

0.449

Alfa

AF:

0.495

Hom.:

48876

Bravo

AF:

0.445

TwinsUK

AF:

0.513

AC:

1904

ALSPAC

AF:

0.513

AC:

1977

ESP6500AA

AF:

0.357

AC:

1347

ESP6500EA

AF:

0.506

AC:

4162

ExAC

AF:

0.484

AC:

58470

Asia WGS

AF:

0.398

AC:

1383

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24604202, 17671174) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

D;D

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.91

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.48

MPC

0.082

ClinPred

0.11

GERP RS

6.0

Varity_R

0.79

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: 16

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