8-40015416-T-G

Variant names:

• chr8-40015416-T-G
• NM_194294.5:c.1038T>G
• IDO2 p.Tyr346*

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_194294.5(IDO2):​c.1038T>G​(p.Tyr346*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IDO2 NM_194294.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194294.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO2	NM_194294.5	MANE Select	c.1038T>G	p.Tyr346*	stop_gained	Exon 11 of 11	NP_919270.3	Q6ZQW0-1
	IDO2	NM_001395206.1		c.1038T>G	p.Tyr346*	stop_gained	Exon 10 of 10	NP_001382135.1	Q6ZQW0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO2	ENST00000502986.4	TSL:5 MANE Select	c.1038T>G	p.Tyr346*	stop_gained	Exon 11 of 11	ENSP00000443432.2	Q6ZQW0-1
	IDO2	ENST00000868807.1		c.819T>G	p.Tyr273*	stop_gained	Exon 8 of 8	ENSP00000538866.1
	IDO2	ENST00000343295.8	TSL:2	n.3289T>G		non_coding_transcript_exon	Exon 11 of 11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.87	D
PhyloP100		0.11
Mutation Taster		=184/16	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-39872935;