rs1061925

Positions:

• chr6-24665779-T-G

Variant summary

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

The ENST00000378198.9(TDP2):​c.251+747A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,120 control chromosomes in the GnomAD database, including 1,964 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 0.15 (1964 hom., cov: 32)
• Consequence: TDP2 ENST00000378198.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDP2	NM_016614.3	c.251+747A>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.251+747A>C		intron_variant		1	NM_016614.3	ENSP00000367440	P1
TDP2	ENST00000341060.3	c.77+340A>C		intron_variant		1		ENSP00000345345
TDP2	ENST00000478507.1	n.319+747A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22907 AN: 152002 Hom.: 1962 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.151 AC: 22929 AN: 152120 Hom.: 1964 Cov.: 32 AF XY: 0.149 AC XY: 11071 AN XY: 74368

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0903

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.0912

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.151

Alfa AF: 0.124 Hom.: 1607

Bravo AF: 0.156

Asia WGS AF: 0.170 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.71
DANN	Benign	0.37

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: rs1061925; hg19: chr6-24666007;