rs3181244

Positions:

• chr6-24651160-G-A

Variant summary

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

The NM_016614.3(TDP2):​c.808-91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,040,718 control chromosomes in the GnomAD database, including 12,049 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 (1447 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10602 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

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 (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDP2	NM_016614.3	c.808-91C>T		intron_variant		ENST00000378198.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDP2	ENST00000378198.9	c.808-91C>T		intron_variant		1	NM_016614.3	P1
TDP2	ENST00000341060.3	c.634-91C>T		intron_variant		1
TDP2	ENST00000478507.1	n.491-91C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19778 AN: 149600 Hom.: 1449 Cov.: 32

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.227

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.146 AC: 129701 AN: 891080 Hom.: 10602 AF XY: 0.149 AC XY: 66907 AN XY: 450082

Gnomad4 AFR exome AF: 0.0877

Gnomad4 AMR exome AF: 0.0984

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.0986

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.132 AC: 19768 AN: 149638 Hom.: 1447 Cov.: 32 AF XY: 0.130 AC XY: 9482 AN XY: 72840

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.138

Alfa AF: 0.132 Hom.: 368

Bravo AF: 0.130

Asia WGS AF: 0.200 AC: 695 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	3.4
DANN	Benign	0.62

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: rs3181244; hg19: chr6-24651388;