rs35446289

Variant names:

• chr8-40015491-AG-A
• rs35446289
• NM_194294.5:c.1116delG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_194294.5(IDO2):​c.1116delG​(p.Pro373LeufsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDO2	NM_194294.5	c.1116delG	p.Pro373LeufsTer5	frameshift_variant	Exon 11 of 11	ENST00000502986.4	NP_919270.3
IDO2	NM_001395206.1	c.1116delG	p.Pro373LeufsTer5	frameshift_variant	Exon 10 of 10		NP_001382135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDO2	ENST00000502986.4	c.1116delG	p.Pro373LeufsTer5	frameshift_variant	Exon 11 of 11	5	NM_194294.5	ENSP00000443432.2
IDO2	ENST00000343295.8	n.3367delG		non_coding_transcript_exon_variant	Exon 11 of 11	2
IDO2	ENST00000418094.1	n.743delG		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs35446289; hg19: chr8-39873010;