rs879255601

chr6-24658572-GG-TT

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_016614.3(TDP2):c.413_414delinsAA(p.Ser138Ter) variant causes a stop gained change. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TDP2 NM_016614.3 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.81

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 6-24658572-GG-TT is Pathogenic according to our data. Variant chr6-24658572-GG-TT is described in ClinVar as [Pathogenic]. Clinvar id is 226425.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDP2	NM_016614.3	c.413_414delinsAA	p.Ser138Ter	stop_gained	3/7	ENST00000378198.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDP2	ENST00000378198.9	c.413_414delinsAA	p.Ser138Ter	stop_gained	3/7	1	NM_016614.3	P1
TDP2	ENST00000341060.3	c.239_240delinsAA	p.Ser80Ter	stop_gained	2/6	1
TDP2	ENST00000478285.1	n.600_601delinsAA		non_coding_transcript_exon_variant	1/3	2
TDP2	ENST00000478507.1	n.320-5420_320-5419delinsAA		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spinocerebellar ataxia, autosomal recessive 23 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 28, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879255601; hg19: chr6-24658800;