rs13152449

Variant names:

• chr4-155914650-A-G
• rs13152449
• NM_005651.4:c.838+216A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005651.4(TDO2):​c.838+216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,178 control chromosomes in the GnomAD database, including 946 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 0.10 (946 hom., cov: 32)
• Consequence: TDO2 NM_005651.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 3 publications found

Genes affected

TDO2 (HGNC:11708): (tryptophan 2,3-dioxygenase) This gene encodes a heme enzyme that plays a critical role in tryptophan metabolism by catalyzing the first and rate-limiting step of the kynurenine pathway. Increased activity of the encoded protein and subsequent kynurenine production may also play a role in cancer through the suppression of antitumor immune responses, and single nucleotide polymorphisms in this gene may be associated with autism. [provided by RefSeq, Feb 2012]

TDO2 Gene-Disease associations (from GenCC):

• familial hypertryptophanemia

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDO2	NM_005651.4	c.838+216A>G		intron_variant	Intron 8 of 11	ENST00000536354.3	NP_005642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDO2	ENST00000536354.3	c.838+216A>G		intron_variant	Intron 8 of 11	1	NM_005651.4	ENSP00000444788.2
TDO2	ENST00000512584.5	n.2348+216A>G		intron_variant	Intron 5 of 8	1
TDO2	ENST00000510293.1	n.94+216A>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15939 AN: 152060 Hom.: 944 Cov.: 32

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0741

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0995

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15948 AN: 152178 Hom.: 946 Cov.: 32 AF XY: 0.107 AC XY: 7945 AN XY: 74408

African (AFR) AF: 0.0936 AC: 3889 AN: 41532

American (AMR) AF: 0.119 AC: 1818 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3470

East Asian (EAS) AF: 0.0743 AC: 385 AN: 5184

South Asian (SAS) AF: 0.165 AC: 797 AN: 4824

European-Finnish (FIN) AF: 0.129 AC: 1372 AN: 10602

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6898 AN: 67954

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.106 Hom.: 458

Bravo AF: 0.102

Asia WGS AF: 0.136 AC: 472 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.37
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13152449; hg19: chr4-156835802;