rs3181245

Positions:

• chr6-24651092-C-G

Variant summary

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

The NM_016614.3(TDP2):​c.808-23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,567,822 control chromosomes in the GnomAD database, including 166,544 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 0.45 (15406 hom., cov: 26)
  • Exomes 𝑓: 0.46 (151138 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP2	NM_016614.3	c.808-23G>C		intron_variant		ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.808-23G>C		intron_variant		1	NM_016614.3	ENSP00000367440	P1
TDP2	ENST00000341060.3	c.634-23G>C		intron_variant		1		ENSP00000345345
TDP2	ENST00000478507.1	n.491-23G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 67321 AN: 148500 Hom.: 15397 Cov.: 26

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.451

GnomAD3 exomes AF: 0.419 AC: 96517 AN: 230294 Hom.: 20891 AF XY: 0.420 AC XY: 52758 AN XY: 125698

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.223

Gnomad SAS exome AF: 0.301

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.491

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.457 AC: 648774 AN: 1419210 Hom.: 151138 Cov.: 27 AF XY: 0.454 AC XY: 319788 AN XY: 705036

Gnomad4 AFR exome AF: 0.457

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.448

GnomAD4 genome AF: 0.453 AC: 67360 AN: 148612 Hom.: 15406 Cov.: 26 AF XY: 0.447 AC XY: 32260 AN XY: 72232

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.455

Alfa AF: 0.475 Hom.: 3196

Bravo AF: 0.449

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3181245; hg19: chr6-24651320; COSMIC: COSV61968291; COSMIC: COSV61968291;