rs10109853

Variant names:

• chr8-40005362-C-T
• rs10109853
• NM_194294.5:c.703C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_194294.5(IDO2):​c.703C>T​(p.Arg235Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,553,334 control chromosomes in the GnomAD database, including 195,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16804 hom., cov: 33)
  • Exomes 𝑓: 0.50 (179000 hom.)
• Consequence: IDO2 NM_194294.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.34
• Publications: 58 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 8-40005362-C-T is Benign according to our data. Variant chr8-40005362-C-T is described in ClinVar as Benign. ClinVar VariationId is 1275323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

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.703C>T	p.Arg235Trp	missense	Exon 9 of 11	NP_919270.3
	IDO2	NM_001395206.1		c.703C>T	p.Arg235Trp	missense	Exon 8 of 10	NP_001382135.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO2	ENST00000502986.4	TSL:5 MANE Select	c.703C>T	p.Arg235Trp	missense	Exon 9 of 11	ENSP00000443432.2
	IDO2	ENST00000868807.1		c.484C>T	p.Arg162Trp	missense	Exon 6 of 8	ENSP00000538866.1
	IDO2	ENST00000343295.8	TSL:2	n.2971-8203C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70106 AN: 151900 Hom.: 16793 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.448

GnomAD2 exomes AF: 0.481 AC: 111843 AN: 232302 AF XY: 0.484

Gnomad AFR exome AF: 0.342

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.233

Gnomad FIN exome AF: 0.560

Gnomad NFE exome AF: 0.496

Gnomad OTH exome AF: 0.490

GnomAD4 exome AF: 0.500 AC: 701099 AN: 1401316 Hom.: 179000 Cov.: 28 AF XY: 0.501 AC XY: 347603 AN XY: 694110

African (AFR) AF: 0.339 AC: 11058 AN: 32610

American (AMR) AF: 0.514 AC: 21258 AN: 41326

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 13084 AN: 24786

East Asian (EAS) AF: 0.264 AC: 10269 AN: 38950

South Asian (SAS) AF: 0.528 AC: 40130 AN: 75950

European-Finnish (FIN) AF: 0.550 AC: 28423 AN: 51648

Middle Eastern (MID) AF: 0.475 AC: 2642 AN: 5566

European-Non Finnish (NFE) AF: 0.509 AC: 546478 AN: 1072668

Other (OTH) AF: 0.480 AC: 27757 AN: 57812

GnomAD4 genome AF: 0.461 AC: 70139 AN: 152018 Hom.: 16804 Cov.: 33 AF XY: 0.463 AC XY: 34422 AN XY: 74302

African (AFR) AF: 0.357 AC: 14811 AN: 41442

American (AMR) AF: 0.465 AC: 7108 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1835 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1309 AN: 5168

South Asian (SAS) AF: 0.544 AC: 2623 AN: 4824

European-Finnish (FIN) AF: 0.582 AC: 6144 AN: 10554

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34850 AN: 67968

Other (OTH) AF: 0.449 AC: 950 AN: 2114

Alfa AF: 0.488 Hom.: 71079

Bravo AF: 0.445

TwinsUK AF: 0.513 AC: 1904

ALSPAC AF: 0.513 AC: 1977

ESP6500AA AF: 0.357 AC: 1347

ESP6500EA AF: 0.506 AC: 4162

ExAC AF: 0.484 AC: 58470

Asia WGS AF: 0.398 AC: 1383 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.91	T
PhyloP100		3.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.48
MPC		0.082
ClinPred		0.11	T
GERP RS		6.0
Varity_R		0.79
gMVP		0.72
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.22		Position offset: 16

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

Other links and lift over

dbSNP: rs10109853; hg19: chr8-39862881; COSMIC: COSV58423701;