rs3181245

Variant names:

• chr6-24651092-C-G
• rs3181245
• NM_016614.3:c.808-23G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-24651092-C-G
• chr6-24651092-C-T

Variant summary

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

The NM_016614.3(TDP2):​c.808-23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,567,822 control chromosomes in the GnomAD database, including 166,544 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 0.45 (15406 hom., cov: 26)
  • Exomes 𝑓: 0.46 (151138 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDP2	NM_016614.3	c.808-23G>C		intron_variant	Intron 6 of 6	ENST00000378198.9	NP_057698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDP2	ENST00000378198.9	c.808-23G>C		intron_variant	Intron 6 of 6	1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.634-23G>C		intron_variant	Intron 5 of 5	1		ENSP00000345345.3
TDP2	ENST00000478507.1	n.491-23G>C		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 67321 AN: 148500 Hom.: 15397 Cov.: 26

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.451

GnomAD2 exomes AF: 0.419 AC: 96517 AN: 230294 AF XY: 0.420

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.491

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.457 AC: 648774 AN: 1419210 Hom.: 151138 Cov.: 27 AF XY: 0.454 AC XY: 319788 AN XY: 705036

African (AFR) AF: 0.457 AC: 14770 AN: 32344

American (AMR) AF: 0.359 AC: 15026 AN: 41866

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 11886 AN: 25060

East Asian (EAS) AF: 0.227 AC: 8890 AN: 39172

South Asian (SAS) AF: 0.295 AC: 24486 AN: 83060

European-Finnish (FIN) AF: 0.409 AC: 20513 AN: 50186

Middle Eastern (MID) AF: 0.485 AC: 2699 AN: 5566

European-Non Finnish (NFE) AF: 0.484 AC: 524150 AN: 1083158

Other (OTH) AF: 0.448 AC: 26354 AN: 58798

GnomAD4 genome AF: 0.453 AC: 67360 AN: 148612 Hom.: 15406 Cov.: 26 AF XY: 0.447 AC XY: 32260 AN XY: 72232

African (AFR) AF: 0.462 AC: 18520 AN: 40098

American (AMR) AF: 0.413 AC: 6162 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1593 AN: 3456

East Asian (EAS) AF: 0.216 AC: 1081 AN: 5008

South Asian (SAS) AF: 0.277 AC: 1297 AN: 4680

European-Finnish (FIN) AF: 0.433 AC: 4207 AN: 9726

Middle Eastern (MID) AF: 0.493 AC: 140 AN: 284

European-Non Finnish (NFE) AF: 0.490 AC: 33041 AN: 67480

Other (OTH) AF: 0.455 AC: 937 AN: 2060

Alfa AF: 0.475 Hom.: 3196

Bravo AF: 0.449

Asia WGS AF: 0.275 AC: 956 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	0.16
DANN	Benign	0.55
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3181245; hg19: chr6-24651320; COSMIC: COSV61968291; COSMIC: COSV61968291;