rs1129644

Variant names:

• chr6-24653148-G-A
• rs1129644
• NM_016614.3:c.642C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24653148-G-A
• chr6-24653148-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016614.3(TDP2):​c.642C>T​(p.Asn214Asn) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 29 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 23

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TDP2	NM_016614.3	c.642C>T	p.Asn214Asn	synonymous_variant	Exon 6 of 7	ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.642C>T	p.Asn214Asn	synonymous_variant	Exon 6 of 7	1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.468C>T	p.Asn156Asn	synonymous_variant	Exon 5 of 6	1		ENSP00000345345.3
TDP2	ENST00000478507.1	n.325C>T		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116603 AN: 152030 Hom.: 45449 Cov.: 32

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

GnomAD2 exomes AF: 0.739 AC: 185623 AN: 251158 AF XY: 0.729

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 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.: 44 AF XY: 0.707 AC XY: 514034 AN XY: 726798

African (AFR) AF: 0.915 AC: 30620 AN: 33466

American (AMR) AF: 0.837 AC: 37445 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 18334 AN: 26128

East Asian (EAS) AF: 0.873 AC: 34637 AN: 39686

South Asian (SAS) AF: 0.713 AC: 61453 AN: 86238

European-Finnish (FIN) AF: 0.634 AC: 33825 AN: 53370

Middle Eastern (MID) AF: 0.775 AC: 4468 AN: 5766

European-Non Finnish (NFE) AF: 0.694 AC: 771152 AN: 1111212

Other (OTH) AF: 0.726 AC: 43853 AN: 60366

GnomAD4 genome AF: 0.767 AC: 116726 AN: 152148 Hom.: 45512 Cov.: 32 AF XY: 0.763 AC XY: 56740 AN XY: 74364

African (AFR) AF: 0.906 AC: 37638 AN: 41524

American (AMR) AF: 0.798 AC: 12204 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2422 AN: 3470

East Asian (EAS) AF: 0.856 AC: 4425 AN: 5172

South Asian (SAS) AF: 0.718 AC: 3469 AN: 4830

European-Finnish (FIN) AF: 0.632 AC: 6676 AN: 10560

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47337 AN: 67986

Other (OTH) AF: 0.746 AC: 1576 AN: 2112

Alfa AF: 0.718 Hom.: 89630

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
PhyloP100		0.044
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1129644; hg19: chr6-24653376; COSMIC: COSV61966248; COSMIC: COSV61966248;