rs4503083

chr8-40015416-T-Achr8-40015416-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_194294.5(IDO2):c.1038T>A(p.Tyr346Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,613,680 control chromosomes in the GnomAD database, including 35,935 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3180 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32755 hom.)
• Consequence: IDO2 NM_194294.5 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Stoplost variant in NM_194294.5 Downstream stopcodon found after 602 codons.
• BP6: Variant 8-40015416-T-A is Benign according to our data. Variant chr8-40015416-T-A is described in ClinVar as [Benign]. Clinvar id is 1229251.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDO2	NM_194294.5	c.1038T>A	p.Tyr346Ter	stop_gained	11/11	ENST00000502986.4
IDO2	NM_001395206.1	c.1038T>A	p.Tyr346Ter	stop_gained	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDO2	ENST00000502986.4	c.1038T>A	p.Tyr346Ter	stop_gained	11/11	5	NM_194294.5	P1
IDO2	ENST00000343295.8	n.3289T>A		non_coding_transcript_exon_variant	11/11	2
IDO2	ENST00000418094.1	n.665T>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29890 AN: 151990 Hom.: 3179 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.227 AC: 56546 AN: 248808 Hom.: 6915 AF XY: 0.227 AC XY: 30665 AN XY: 134968

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.378

Gnomad SAS exome AF: 0.231

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.208 AC: 304115 AN: 1461576 Hom.: 32755 Cov.: 49 AF XY: 0.209 AC XY: 152000 AN XY: 727050

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.197 AC: 29895 AN: 152104 Hom.: 3180 Cov.: 32 AF XY: 0.200 AC XY: 14865 AN XY: 74360

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.214

Alfa AF: 0.199 Hom.: 987

Bravo AF: 0.200

TwinsUK AF: 0.201 AC: 744

ALSPAC AF: 0.213 AC: 821

ESP6500AA AF: 0.110 AC: 458

ESP6500EA AF: 0.207 AC: 1743

ExAC AF: 0.225 AC: 27248

Asia WGS AF: 0.279 AC: 969 AN: 3478

EpiCase AF: 0.207

EpiControl AF: 0.213

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

Jan 10, 2019

This variant is associated with the following publications: (PMID: 25541686, 17671174) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.59
Cadd	Pathogenic	35
Dann	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.86	D
MutationTaster	Benign	9.4e-14	P;P
Vest4		0.89
GERP RS		-2.2

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: rs4503083; hg19: chr8-39872935; COSMIC: COSV58423710;