rs3756815

Positions:

• chr6-24665966-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016614.3(TDP2):​c.251+560C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0789 in 1,046,456 control chromosomes in the GnomAD database, including 7,598 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 0.13 (2252 hom., cov: 32)
  • Exomes 𝑓: 0.071 (5346 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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	Protein	UniProt
TDP2	NM_016614.3	c.251+560C>G		intron_variant		ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.251+560C>G		intron_variant		1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.77+153C>G		intron_variant		1		ENSP00000345345.3
TDP2	ENST00000478507.1	n.319+560C>G		intron_variant		5
TDP2	ENST00000480495.1	n.*21C>G		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19284 AN: 151926 Hom.: 2241 Cov.: 32

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: 0.0154

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0707 AC: 63227 AN: 894410 Hom.: 5346 Cov.: 12 AF XY: 0.0706 AC XY: 30825 AN XY: 436650

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.0452

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0132

Gnomad4 NFE exome AF: 0.0473

Gnomad4 OTH exome AF: 0.0982

GnomAD4 genome AF: 0.127 AC: 19328 AN: 152046 Hom.: 2252 Cov.: 32 AF XY: 0.130 AC XY: 9696 AN XY: 74334

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0154

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0760 Hom.: 137

Bravo AF: 0.151

Asia WGS AF: 0.271 AC: 944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.35

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

Other links and lift over

dbSNP: rs3756815; hg19: chr6-24666194;