NM_016614.3:c.808-91C>T

Variant names:

• chr6-24651160-G-A
• rs3181244
• NM_016614.3:c.808-91C>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.808-91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,040,718 control chromosomes in the GnomAD database, including 12,049 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 (1447 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10602 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDP2	NM_016614.3	MANE Select	c.808-91C>T		intron	N/A	NP_057698.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDP2	ENST00000378198.9	TSL:1 MANE Select	c.808-91C>T		intron	N/A	ENSP00000367440.4
	TDP2	ENST00000341060.3	TSL:1	c.634-91C>T		intron	N/A	ENSP00000345345.3
	TDP2	ENST00000874524.1		c.802-91C>T		intron	N/A	ENSP00000544583.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19778 AN: 149600 Hom.: 1449 Cov.: 32

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.227

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.146 AC: 129701 AN: 891080 Hom.: 10602 AF XY: 0.149 AC XY: 66907 AN XY: 450082

African (AFR) AF: 0.0877 AC: 1819 AN: 20744

American (AMR) AF: 0.0984 AC: 2120 AN: 21550

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 2604 AN: 16758

East Asian (EAS) AF: 0.175 AC: 6149 AN: 35200

South Asian (SAS) AF: 0.231 AC: 12812 AN: 55370

European-Finnish (FIN) AF: 0.0986 AC: 3497 AN: 35466

Middle Eastern (MID) AF: 0.213 AC: 649 AN: 3054

European-Non Finnish (NFE) AF: 0.142 AC: 93944 AN: 662364

Other (OTH) AF: 0.151 AC: 6107 AN: 40574

GnomAD4 genome AF: 0.132 AC: 19768 AN: 149638 Hom.: 1447 Cov.: 32 AF XY: 0.130 AC XY: 9482 AN XY: 72840

African (AFR) AF: 0.0968 AC: 3928 AN: 40574

American (AMR) AF: 0.119 AC: 1790 AN: 15024

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3466

East Asian (EAS) AF: 0.164 AC: 844 AN: 5142

South Asian (SAS) AF: 0.250 AC: 1188 AN: 4756

European-Finnish (FIN) AF: 0.0969 AC: 938 AN: 9678

Middle Eastern (MID) AF: 0.229 AC: 65 AN: 284

European-Non Finnish (NFE) AF: 0.146 AC: 9887 AN: 67742

Other (OTH) AF: 0.138 AC: 284 AN: 2062

Alfa AF: 0.136 Hom.: 629

Bravo AF: 0.130

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		-0.97
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: rs3181244; hg19: chr6-24651388; COSMIC: COSV107436237; COSMIC: COSV107436237;