rs35212142

Positions:

• chr8-40005374-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_194294.5(IDO2):​c.715T>A​(p.Ser239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,561,968 control chromosomes in the GnomAD database, including 892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (69 hom., cov: 33)
  • Exomes 𝑓: 0.031 (823 hom.)
• Consequence: IDO2 NM_194294.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015613109).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0238 (3620/152348) while in subpopulation NFE AF= 0.0375 (2549/68034). AF 95% confidence interval is 0.0363. There are 69 homozygotes in gnomad4. There are 1715 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDO2	NM_194294.5	c.715T>A	p.Ser239Thr	missense_variant	9/11	ENST00000502986.4
IDO2	NM_001395206.1	c.715T>A	p.Ser239Thr	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDO2	ENST00000502986.4	c.715T>A	p.Ser239Thr	missense_variant	9/11	5	NM_194294.5	P1
IDO2	ENST00000343295.8	n.2971-8191T>A		intron_variant, non_coding_transcript_variant		2
IDO2	ENST00000418094.1	n.347-8191T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3620 AN: 152230 Hom.: 69 Cov.: 33

Gnomad AFR AF: 0.00644

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0203 AC: 4824 AN: 238208 Hom.: 88 AF XY: 0.0203 AC XY: 2627 AN XY: 129262

Gnomad AFR exome AF: 0.00509

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.00714

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00539

Gnomad FIN exome AF: 0.0315

Gnomad NFE exome AF: 0.0314

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0310 AC: 43720 AN: 1409620 Hom.: 823 Cov.: 26 AF XY: 0.0306 AC XY: 21365 AN XY: 699254

Gnomad4 AFR exome AF: 0.00489

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.00650

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00472

Gnomad4 FIN exome AF: 0.0303

Gnomad4 NFE exome AF: 0.0366

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.0238 AC: 3620 AN: 152348 Hom.: 69 Cov.: 33 AF XY: 0.0230 AC XY: 1715 AN XY: 74494

Gnomad4 AFR AF: 0.00642

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.00664

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.0370

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.0322 Hom.: 78

Bravo AF: 0.0213

TwinsUK AF: 0.0356 AC: 132

ALSPAC AF: 0.0392 AC: 151

ESP6500AA AF: 0.00614 AC: 23

ESP6500EA AF: 0.0309 AC: 254

ExAC AF: 0.0220 AC: 2658

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;D
MetaRNN	Benign	0.016	T;T
MetaSVM	Benign	-0.83	T
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.012	D;D
Vest4		0.20
MPC		0.026
ClinPred		0.046	T
GERP RS		3.6
Varity_R		0.46
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs35212142; hg19: chr8-39862893; COSMIC: COSV100584699;