rs3087943

Variant names:

• chr6-24650533-A-G
• rs3087943
• NM_016614.3:c.*255T>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.*255T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 461,264 control chromosomes in the GnomAD database, including 7,113 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 0.18 (2647 hom., cov: 32)
  • Exomes 𝑓: 0.16 (4466 hom.)
• Consequence: TDP2 NM_016614.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 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.*255T>C		3_prime_UTR	Exon 7 of 7	NP_057698.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDP2	ENST00000378198.9	TSL:1 MANE Select	c.*255T>C		3_prime_UTR	Exon 7 of 7	ENSP00000367440.4
	TDP2	ENST00000341060.3	TSL:1	c.*255T>C		3_prime_UTR	Exon 6 of 6	ENSP00000345345.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27451 AN: 152142 Hom.: 2649 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.162 AC: 50206 AN: 309004 Hom.: 4466 Cov.: 3 AF XY: 0.160 AC XY: 25952 AN XY: 162456

African (AFR) AF: 0.235 AC: 2098 AN: 8920

American (AMR) AF: 0.160 AC: 1647 AN: 10316

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 1692 AN: 9998

East Asian (EAS) AF: 0.0677 AC: 1376 AN: 20314

South Asian (SAS) AF: 0.115 AC: 3438 AN: 29886

European-Finnish (FIN) AF: 0.111 AC: 2000 AN: 18054

Middle Eastern (MID) AF: 0.157 AC: 215 AN: 1368

European-Non Finnish (NFE) AF: 0.181 AC: 34638 AN: 191786

Other (OTH) AF: 0.169 AC: 3102 AN: 18362

GnomAD4 genome AF: 0.180 AC: 27470 AN: 152260 Hom.: 2647 Cov.: 32 AF XY: 0.176 AC XY: 13073 AN XY: 74454

African (AFR) AF: 0.232 AC: 9643 AN: 41536

American (AMR) AF: 0.167 AC: 2556 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3470

East Asian (EAS) AF: 0.0404 AC: 210 AN: 5192

South Asian (SAS) AF: 0.113 AC: 545 AN: 4828

European-Finnish (FIN) AF: 0.112 AC: 1188 AN: 10616

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12235 AN: 68008

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.180 Hom.: 5092

Bravo AF: 0.186

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.097
DANN	Benign	0.43
PhyloP100		-0.40
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: rs3087943; hg19: chr6-24650761;