rs3033236

Positions:

• chr6-24657625-CTATTAA-C
• chr6-24657625-CTATTAA-CTATTAATATTAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016614.3(TDP2):​c.517+181_517+186delTTAATA 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 151,944 control chromosomes in the GnomAD database, including 2,075 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2075 hom., cov: 29)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP2	NM_016614.3	c.517+181_517+186delTTAATA		intron_variant		ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.517+181_517+186delTTAATA		intron_variant		1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.343+181_343+186delTTAATA		intron_variant		1		ENSP00000345345.3
TDP2	ENST00000478285.1	n.704+181_704+186delTTAATA		intron_variant		2
TDP2	ENST00000478507.1	n.320-4478_320-4473delTTAATA		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24606 AN: 151826 Hom.: 2077 Cov.: 29

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.173

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24604 AN: 151944 Hom.: 2075 Cov.: 29 AF XY: 0.161 AC XY: 11951 AN XY: 74260

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.171

Alfa AF: 0.146 Hom.: 204

Bravo AF: 0.165

Asia WGS AF: 0.242 AC: 834 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3033236; hg19: chr6-24657853;