rs2143340

Variant names:

• chr6-24658843-A-C
• rs2143340
• NM_016614.3:c.252-109T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-24658843-A-C
• chr6-24658843-A-G
• chr6-24658843-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016614.3(TDP2):​c.252-109T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000841 in 950,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: TDP2 NM_016614.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDP2	NM_016614.3	c.252-109T>G		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.252-109T>G		intron_variant	Intron 2 of 6	1	NM_016614.3	ENSP00000367440.4
TDP2	ENST00000341060.3	c.78-109T>G		intron_variant	Intron 1 of 5	1		ENSP00000345345.3
TDP2	ENST00000478285.1	n.330T>G		non_coding_transcript_exon_variant	Exon 1 of 3	2
TDP2	ENST00000478507.1	n.320-5690T>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000841 AC: 8 AN: 950874 Hom.: 0 Cov.: 12 AF XY: 0.0000125 AC XY: 6 AN XY: 480658

African (AFR) AF: 0.00 AC: 0 AN: 21550

American (AMR) AF: 0.00 AC: 0 AN: 26970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17756

East Asian (EAS) AF: 0.00 AC: 0 AN: 34494

South Asian (SAS) AF: 0.000135 AC: 8 AN: 59382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4320

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 704222

Other (OTH) AF: 0.00 AC: 0 AN: 42620

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.81
PhyloP100		0.26

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: rs2143340; hg19: chr6-24659071;