8-39949242-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_194294.5(IDO2):c.77G>C(p.Gly26Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IDO2 NM_194294.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDO2	NM_194294.5	c.77G>C	p.Gly26Ala	missense_variant	2/11	ENST00000502986.4
IDO2	NM_001395206.1	c.77G>C	p.Gly26Ala	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDO2	ENST00000502986.4	c.77G>C	p.Gly26Ala	missense_variant	2/11	5	NM_194294.5	P1
	ENST00000517623.1	n.255+38136C>G		intron_variant, non_coding_transcript_variant		4
IDO2	ENST00000343295.8	n.699G>C		non_coding_transcript_exon_variant	2/11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.116G>C (p.G39A) alteration is located in exon 2 (coding exon 2) of the IDO2 gene. This alteration results from a G to C substitution at nucleotide position 116, causing the glycine (G) at amino acid position 39 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.28	D
MutationTaster	Benign	0.85	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.017	D;D
Vest4		0.93
MutPred		0.96		Gain of phosphorylation at Y38 (P = 0.2125);.;
MVP		0.87
MPC		0.079
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.89
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-39806761;