6-24654466-TTG-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016614.3(TDP2):c.580_581del(p.Gln194ArgfsTer25) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
TDP2
NM_016614.3 frameshift
NM_016614.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.29
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-24654466-TTG-T is Pathogenic according to our data. Variant chr6-24654466-TTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 2598969.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TDP2 | NM_016614.3 | c.580_581del | p.Gln194ArgfsTer25 | frameshift_variant | 5/7 | ENST00000378198.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TDP2 | ENST00000378198.9 | c.580_581del | p.Gln194ArgfsTer25 | frameshift_variant | 5/7 | 1 | NM_016614.3 | P1 | |
TDP2 | ENST00000341060.3 | c.406_407del | p.Gln136ArgfsTer25 | frameshift_variant | 4/6 | 1 | |||
TDP2 | ENST00000478285.1 | n.767_768del | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
TDP2 | ENST00000478507.1 | n.320-1315_320-1314del | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2023 | The c.580_581delCA (p.Q194Rfs*25) alteration, located in exon 5 (coding exon 5) of the TDP2 gene, consists of a deletion of 2 nucleotides from position 580 to 581, causing a translational frameshift with a predicted alternate stop codon after 25 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.