rs2143340

chr6-24658843-A-Gchr6-24658843-A-T

Variant summary

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

The NM_016614.3(TDP2):c.252-109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,101,538 control chromosomes in the GnomAD database, including 14,973 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 0.16 (2021 hom., cov: 32)
  • Exomes 𝑓: 0.16 (12952 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDP2	NM_016614.3	c.252-109T>C		intron_variant		ENST00000378198.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDP2	ENST00000378198.9	c.252-109T>C		intron_variant		1	NM_016614.3	P1
TDP2	ENST00000341060.3	c.78-109T>C		intron_variant		1
TDP2	ENST00000478285.1	n.330T>C		non_coding_transcript_exon_variant	1/3	2
TDP2	ENST00000478507.1	n.320-5690T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24060 AN: 152058 Hom.: 2021 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.163 AC: 154593 AN: 949360 Hom.: 12952 Cov.: 12 AF XY: 0.166 AC XY: 79523 AN XY: 479890

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.158 AC: 24054 AN: 152178 Hom.: 2021 Cov.: 32 AF XY: 0.156 AC XY: 11645 AN XY: 74416

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.162

Alfa AF: 0.150 Hom.: 3014

Bravo AF: 0.159

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.8
Dann	Benign	0.84

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: rs2143340; hg19: chr6-24659071;