Variant rs1129644 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_016614.3(TDP2):c.642C>T(p.Asn214=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,613,100 control chromosomes in the GnomAD database, including 415,311 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 0.77 ( 45512 hom., cov: 32)

Exomes 𝑓: 0.71 ( 369799 hom. )

Consequence

TDP2
NM_016614.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0440

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=0.044 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 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.642C>T	p.Asn214=	synonymous_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.642C>T	p.Asn214=	synonymous_variant	6/7	1	NM_016614.3	P1	O95551-1
TDP2	ENST00000341060.3 linkuse as main transcript	c.468C>T	p.Asn156=	synonymous_variant	5/6	1
TDP2	ENST00000478507.1 linkuse as main transcript	n.325C>T		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.767

AC:

116603

AN:

152030

Hom.:

45449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.798

Gnomad ASJ

AF:

0.698

Gnomad EAS

AF:

0.856

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.696

Gnomad OTH

AF:

0.743

GnomAD3 exomes

AF:

0.739

AC:

185623

AN:

251158

Hom.:

69554

AF XY:

0.729

AC XY:

98986

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.911

Gnomad AMR exome

AF:

0.845

Gnomad ASJ exome

AF:

0.707

Gnomad EAS exome

AF:

0.844

Gnomad SAS exome

AF:

0.709

Gnomad FIN exome

AF:

0.628

Gnomad NFE exome

AF:

0.698

Gnomad OTH exome

AF:

0.726

GnomAD4 exome

AF:

0.709

AC:

1035787

AN:

1460952

Hom.:

369799

Cov.:

AF XY:

0.707

AC XY:

514034

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.915

Gnomad4 AMR exome

AF:

0.837

Gnomad4 ASJ exome

AF:

0.702

Gnomad4 EAS exome

AF:

0.873

Gnomad4 SAS exome

AF:

0.713

Gnomad4 FIN exome

AF:

0.634

Gnomad4 NFE exome

AF:

0.694

Gnomad4 OTH exome

AF:

0.726

GnomAD4 genome

AF:

0.767

AC:

116726

AN:

152148

Hom.:

45512

Cov.:

AF XY:

0.763

AC XY:

56740

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.906

Gnomad4 AMR

AF:

0.798

Gnomad4 ASJ

AF:

0.698

Gnomad4 EAS

AF:

0.856

Gnomad4 SAS

AF:

0.718

Gnomad4 FIN

AF:

0.632

Gnomad4 NFE

AF:

0.696

Gnomad4 OTH

AF:

0.746

Alfa

AF:

0.713

Hom.:

66837

Bravo

AF:

0.789

Asia WGS

AF:

0.792

AC:

2752

AN:

3478

EpiCase

AF:

0.695

EpiControl

AF:

0.707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.5

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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