rs2294691

chr6-24652615-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.807+368A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,046 control chromosomes in the GnomAD database, including 2,252 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 (2252 hom., cov: 32)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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 (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDP2	NM_016614.3	c.807+368A>G		intron_variant		ENST00000378198.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDP2	ENST00000378198.9	c.807+368A>G		intron_variant		1	NM_016614.3	P1
TDP2	ENST00000341060.3	c.633+368A>G		intron_variant		1
TDP2	ENST00000478507.1	n.490+368A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19411 AN: 151928 Hom.: 2241 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.128 AC: 19454 AN: 152046 Hom.: 2252 Cov.: 32 AF XY: 0.131 AC XY: 9755 AN XY: 74360

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.0435

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0840 Hom.: 167

Bravo AF: 0.152

Asia WGS AF: 0.270 AC: 940 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	14
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs2294691; hg19: chr6-24652843;