rs2056999

chr6-24661283-T-C

Variant summary

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

The NM_016614.3(TDP2):c.252-2549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,152 control chromosomes in the GnomAD database, including 45,540 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 0.77 (45540 hom., cov: 31)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDP2	NM_016614.3	c.252-2549A>G		intron_variant		ENST00000378198.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDP2	ENST00000378198.9	c.252-2549A>G		intron_variant		1	NM_016614.3	P1
TDP2	ENST00000341060.3	c.78-2549A>G		intron_variant		1
TDP2	ENST00000478507.1	n.319+5243A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116620 AN: 152034 Hom.: 45477 Cov.: 31

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.767 AC: 116743 AN: 152152 Hom.: 45540 Cov.: 31 AF XY: 0.763 AC XY: 56746 AN XY: 74374

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.744

Alfa AF: 0.748 Hom.: 7677

Bravo AF: 0.790

Asia WGS AF: 0.792 AC: 2752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.92
Dann	Benign	0.51

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: rs2056999; hg19: chr6-24661511;