rs1061925

Variant names:

• chr6-24665779-T-G
• rs1061925
• NM_016614.3:c.251+747A>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.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 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 9 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 (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDP2	NM_016614.3	c.251+747A>C		intron_variant	Intron 2 of 6	ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.251+747A>C		intron_variant	Intron 2 of 6	1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.77+340A>C		intron_variant	Intron 1 of 5	1		ENSP00000345345.3
TDP2	ENST00000478507.1	n.319+747A>C		intron_variant	Intron 2 of 3	5
TDP2	ENST00000480495.1	n.*208A>C		downstream_gene_variant		1

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

African (AFR) AF: 0.237 AC: 9836 AN: 41462

American (AMR) AF: 0.116 AC: 1770 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3470

East Asian (EAS) AF: 0.0903 AC: 467 AN: 5172

South Asian (SAS) AF: 0.241 AC: 1158 AN: 4814

European-Finnish (FIN) AF: 0.0912 AC: 966 AN: 10592

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7647 AN: 68006

Other (OTH) AF: 0.151 AC: 318 AN: 2108

Alfa AF: 0.125 Hom.: 1937

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
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs1061925; hg19: chr6-24666007;