NM_016614.3:c.518-1193G>C

Variant names:

• chr6-24655723-C-G
• rs3212234
• NM_016614.3:c.518-1193G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016614.3(TDP2):​c.518-1193G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,196 control chromosomes in the GnomAD database, including 2,261 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 (2261 hom., cov: 32)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 23

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• 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 rank	MANE	Protein	UniProt
TDP2	NM_016614.3	c.518-1193G>C		intron_variant	Intron 4 of 6	ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.518-1193G>C		intron_variant	Intron 4 of 6	1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.344-1193G>C		intron_variant	Intron 3 of 5	1		ENSP00000345345.3
TDP2	ENST00000478285.1	n.705-1193G>C		intron_variant	Intron 2 of 2	2
TDP2	ENST00000478507.1	n.320-2570G>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19317 AN: 152078 Hom.: 2250 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.0469

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.127 AC: 19360 AN: 152196 Hom.: 2261 Cov.: 32 AF XY: 0.131 AC XY: 9722 AN XY: 74410

African (AFR) AF: 0.216 AC: 8968 AN: 41494

American (AMR) AF: 0.256 AC: 3913 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 163 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2326 AN: 5172

South Asian (SAS) AF: 0.143 AC: 688 AN: 4824

European-Finnish (FIN) AF: 0.0154 AC: 163 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0418 AC: 2840 AN: 68018

Other (OTH) AF: 0.128 AC: 271 AN: 2110

Alfa AF: 0.0166 Hom.: 7

Bravo AF: 0.151

Asia WGS AF: 0.271 AC: 942 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	4.1
DANN	Benign	0.80
PhyloP100		-0.018
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3212234; hg19: chr6-24655951;