dbSNP rs35212142: IDO2:p.Ser239Thr (chr8-40005374-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

18 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDO2	NM_194294.5 link	c.715T>A	p.Ser239Thr	missense_variant	Exon 9 of 11	ENST00000502986.4	NP_919270.3	Q6ZQW0
IDO2	NM_001395206.1 link	c.715T>A	p.Ser239Thr	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.715T>A	p.Ser239Thr	missense_variant	Exon 9 of 11	5	NM_194294.5	ENSP00000443432.2	Q6ZQW0
IDO2	ENST00000343295.8 link	n.2971-8191T>A		intron_variant	Intron 9 of 10	2
IDO2	ENST00000418094.1 link	n.347-8191T>A		intron_variant	Intron 2 of 3	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

GnomAD2 exomes

AF:

0.0203

AC:

4824

AN:

238208

AF XY:

0.0203

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 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

African (AFR)

AF:

0.00489

AC:

161

AN:

32928

American (AMR)

AF:

0.0110

AC:

468

AN:

42488

Ashkenazi Jewish (ASJ)

AF:

0.00650

AC:

163

AN:

25078

East Asian (EAS)

AF:

0.00

AC:

AN:

39260

South Asian (SAS)

AF:

0.00472

AC:

366

AN:

77536

European-Finnish (FIN)

AF:

0.0303

AC:

1577

AN:

51980

Middle Eastern (MID)

AF:

0.0164

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.0366

AC:

39360

AN:

1076652

Other (OTH)

AF:

0.0264

AC:

1533

AN:

58096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

1629

3257

4886

6514

8143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1508

3016

4524

6032

7540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0238

AC:

3620

AN:

152348

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1715

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00642

AC:

267

AN:

41580

American (AMR)

AF:

0.0181

AC:

277

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00664

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00600

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0370

AC:

393

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0375

AC:

2549

AN:

68034

Other (OTH)

AF:

0.0217

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

190

379

569

758

948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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

PhyloP100

3.5

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

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over