rs4736794

Variant names:

• chr8-39982715-A-G
• rs4736794
• NM_194294.5:c.379A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 11/19 in silico tools predict 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.11
• Publications: 23 publications found

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]

ENSG00000253939 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1265377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
IDO2	NM_194294.5	c.379A>G	p.Ile127Val	missense_variant	Exon 5 of 11	ENST00000502986.4	NP_919270.3
IDO2	NM_001395206.1	c.379A>G	p.Ile127Val	missense_variant	Exon 4 of 10		NP_001382135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDO2	ENST00000502986.4	c.379A>G	p.Ile127Val	missense_variant	Exon 5 of 11	5	NM_194294.5	ENSP00000443432.2
IDO2	ENST00000343295.8	n.1001A>G		non_coding_transcript_exon_variant	Exon 5 of 11	2
ENSG00000253939	ENST00000517623.1	n.255+4663T>C		intron_variant	Intron 2 of 2	4

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

GnomAD2 exomes AF: 0.140 AC: 34332 AN: 244976 AF XY: 0.142

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 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

African (AFR) AF: 0.0267 AC: 893 AN: 33426

American (AMR) AF: 0.201 AC: 8892 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2790 AN: 25988

East Asian (EAS) AF: 0.319 AC: 12637 AN: 39582

South Asian (SAS) AF: 0.193 AC: 16471 AN: 85236

European-Finnish (FIN) AF: 0.119 AC: 6348 AN: 53286

Middle Eastern (MID) AF: 0.189 AC: 1088 AN: 5754

European-Non Finnish (NFE) AF: 0.0853 AC: 94706 AN: 1110000

Other (OTH) AF: 0.120 AC: 7230 AN: 60234

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

African (AFR) AF: 0.0320 AC: 1331 AN: 41558

American (AMR) AF: 0.189 AC: 2889 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1762 AN: 5174

South Asian (SAS) AF: 0.195 AC: 939 AN: 4814

European-Finnish (FIN) AF: 0.116 AC: 1229 AN: 10596

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6208 AN: 68010

Other (OTH) AF: 0.128 AC: 271 AN: 2114

Alfa AF: 0.103 Hom.: 2744

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 30, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		5.1
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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