chr6-24650833-A-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_016614.3(TDP2):c.1044T>G(p.Pro348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,614,136 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00097 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00086 ( 4 hom. )
Consequence
TDP2
NM_016614.3 synonymous
NM_016614.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.54
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 6-24650833-A-C is Benign according to our data. Variant chr6-24650833-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656287.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-24650833-A-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.54 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000971 (148/152344) while in subpopulation AMR AF= 0.00118 (18/15302). AF 95% confidence interval is 0.000852. There are 0 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TDP2 | NM_016614.3 | c.1044T>G | p.Pro348= | synonymous_variant | 7/7 | ENST00000378198.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TDP2 | ENST00000378198.9 | c.1044T>G | p.Pro348= | synonymous_variant | 7/7 | 1 | NM_016614.3 | P1 | |
TDP2 | ENST00000341060.3 | c.870T>G | p.Pro290= | synonymous_variant | 6/6 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000966 AC: 147AN: 152226Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00103 AC: 259AN: 251420Hom.: 3 AF XY: 0.00103 AC XY: 140AN XY: 135888
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GnomAD4 exome AF: 0.000864 AC: 1263AN: 1461792Hom.: 4 Cov.: 32 AF XY: 0.000868 AC XY: 631AN XY: 727206
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | TDP2: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at