Variant rs2294689 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016614.3(TDP2):c.745C>G(p.Gln249Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 1,613,784 control chromosomes in the GnomAD database, including 12,996 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 2259 hom., cov: 32)

Exomes 𝑓: 0.077 ( 10737 hom. )

Consequence

TDP2
NM_016614.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.07

Variant links:

Genes affected

TDP2 (HGNC:17768): (tyrosyl-DNA phosphodiesterase 2) This gene encodes a member of a superfamily of divalent cation-dependent phosphodiesterases. The encoded protein associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor associated factors (TRAFs), and inhibits nuclear factor-kappa-B activation. This protein has sequence and structural similarities with APE1 endonuclease, which is involved in both DNA repair and the activation of transcription factors. [provided by RefSeq, Jul 2008]

TDP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039203465).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDP2	NM_016614.3 linkuse as main transcript	c.745C>G	p.Gln249Glu	missense_variant	6/7	ENST00000378198.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDP2	ENST00000378198.9 linkuse as main transcript	c.745C>G	p.Gln249Glu	missense_variant	6/7	1	NM_016614.3	P1	O95551-1
TDP2	ENST00000341060.3 linkuse as main transcript	c.571C>G	p.Gln191Glu	missense_variant	5/6	1
TDP2	ENST00000478507.1 linkuse as main transcript	n.428C>G		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19295

AN:

151992

Hom.:

2248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.139

AC:

34960

AN:

251338

Hom.:

5387

AF XY:

0.125

AC XY:

16967

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.0515

Gnomad EAS exome

AF:

0.436

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0159

Gnomad NFE exome

AF:

0.0417

Gnomad OTH exome

AF:

0.0992

GnomAD4 exome

AF:

0.0774

AC:

113167

AN:

1461674

Hom.:

10737

Cov.:

AF XY:

0.0765

AC XY:

55611

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.0481

Gnomad4 EAS exome

AF:

0.442

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0147

Gnomad4 NFE exome

AF:

0.0474

Gnomad4 OTH exome

AF:

0.0963

GnomAD4 genome

AF:

0.127

AC:

19338

AN:

152110

Hom.:

2259

Cov.:

AF XY:

0.131

AC XY:

9711

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.0470

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.0418

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0644

Hom.:

600

Bravo

AF:

0.151

TwinsUK

AF:

0.0475

AC:

176

ALSPAC

AF:

0.0566

AC:

218

ESP6500AA

AF:

0.204

AC:

897

ESP6500EA

AF:

0.0443

AC:

381

ExAC

AF:

0.130

AC:

15769

Asia WGS

AF:

0.271

AC:

944

AN:

3478

EpiCase

AF:

0.0412

EpiControl

AF:

0.0440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.045

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.18

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.24

Sift

Benign

0.30

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.091

B;.

Vest4

0.11

MPC

0.19

ClinPred

0.011

GERP RS

5.3

Varity_R

0.18

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over