rs3033236

Variant names:

• chr6-24657625-CTATTAA-C
• rs3033236
• NM_016614.3:c.517+181_517+186delTTAATA

Your query was ambiguous. Multiple possible variants found:

• chr6-24657625-CTATTAA-C
• chr6-24657625-CTATTAA-CTATTAATATTAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_016614.3(TDP2):​c.517+181_517+186delTTAATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,944 control chromosomes in the GnomAD database, including 2,075 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2075 hom., cov: 29)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016614.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDP2	NM_016614.3	MANE Select	c.517+181_517+186delTTAATA		intron	N/A	NP_057698.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDP2	ENST00000378198.9	TSL:1 MANE Select	c.517+181_517+186delTTAATA		intron	N/A	ENSP00000367440.4
	TDP2	ENST00000341060.3	TSL:1	c.343+181_343+186delTTAATA		intron	N/A	ENSP00000345345.3
	TDP2	ENST00000478285.1	TSL:2	n.704+181_704+186delTTAATA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24606 AN: 151826 Hom.: 2077 Cov.: 29

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.162 AC: 24604 AN: 151944 Hom.: 2075 Cov.: 29 AF XY: 0.161 AC XY: 11951 AN XY: 74260

African (AFR) AF: 0.180 AC: 7452 AN: 41432

American (AMR) AF: 0.143 AC: 2177 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1087 AN: 5164

South Asian (SAS) AF: 0.265 AC: 1275 AN: 4806

European-Finnish (FIN) AF: 0.116 AC: 1223 AN: 10554

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10089 AN: 67936

Other (OTH) AF: 0.171 AC: 361 AN: 2108

Alfa AF: 0.146 Hom.: 204

Bravo AF: 0.165

Asia WGS AF: 0.242 AC: 834 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3033236; hg19: chr6-24657853;