rs4736794

chr8-39982715-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_194294.5(IDO2):c.379A>G(p.Ile127Val) variant causes a missense change. The variant allele was found at a frequency of 0.103 in 1,610,022 control chromosomes in the GnomAD database, including 11,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1160 hom., cov: 32)
  • Exomes 𝑓: 0.10 (10145 hom.)
• Consequence: IDO2 NM_194294.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.11

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00180915).
• BP6: Variant 8-39982715-A-G is Benign according to our data. Variant chr8-39982715-A-G is described in ClinVar as [Benign]. Clinvar id is 1265377.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDO2	NM_194294.5	c.379A>G	p.Ile127Val	missense_variant	5/11	ENST00000502986.4
IDO2	NM_001395206.1	c.379A>G	p.Ile127Val	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDO2	ENST00000502986.4	c.379A>G	p.Ile127Val	missense_variant	5/11	5	NM_194294.5	P1
	ENST00000517623.1	n.255+4663T>C		intron_variant, non_coding_transcript_variant		4
IDO2	ENST00000343295.8	n.1001A>G		non_coding_transcript_exon_variant	5/11	2

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15217 AN: 152094 Hom.: 1162 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.140 AC: 34332 AN: 244976 Hom.: 3273 AF XY: 0.142 AC XY: 18814 AN XY: 132696

Gnomad AFR exome AF: 0.0271

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.361

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.0950

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.104 AC: 151055 AN: 1457810 Hom.: 10145 Cov.: 30 AF XY: 0.107 AC XY: 77378 AN XY: 724884

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.0853

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.100 AC: 15220 AN: 152212 Hom.: 1160 Cov.: 32 AF XY: 0.106 AC XY: 7918 AN XY: 74426

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.128

Alfa AF: 0.103 Hom.: 1991

Bravo AF: 0.104

TwinsUK AF: 0.0771 AC: 286

ALSPAC AF: 0.0952 AC: 367

ESP6500AA AF: 0.0305 AC: 115

ESP6500EA AF: 0.0949 AC: 780

ExAC AF: 0.136 AC: 16459

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	22
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.0061	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.016	P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.20
Sift	Benign	0.041	D;D
Sift4G	Benign	0.15	T;T
Vest4		0.12
MPC		0.042
ClinPred		0.036	T
GERP RS		5.3
Varity_R		0.12
gMVP		0.090

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

Other links and lift over

dbSNP: rs4736794; hg19: chr8-39840234; COSMIC: COSV58423692;