chr6-24653017-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_016614.3(TDP2):āc.773T>Cā(p.Ile258Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I258V) has been classified as Likely benign.
Frequency
Consequence
NM_016614.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TDP2 | NM_016614.3 | c.773T>C | p.Ile258Thr | missense_variant | 6/7 | ENST00000378198.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TDP2 | ENST00000378198.9 | c.773T>C | p.Ile258Thr | missense_variant | 6/7 | 1 | NM_016614.3 | P1 | |
TDP2 | ENST00000341060.3 | c.599T>C | p.Ile200Thr | missense_variant | 5/6 | 1 | |||
TDP2 | ENST00000478507.1 | n.456T>C | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251306Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135836
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461676Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 727158
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2023 | The c.773T>C (p.I258T) alteration is located in exon 6 (coding exon 6) of the TDP2 gene. This alteration results from a T to C substitution at nucleotide position 773, causing the isoleucine (I) at amino acid position 258 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at