17-40390129-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001067.4(TOP2A):āc.4303A>Gā(p.Arg1435Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,610,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001067.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TOP2A | NM_001067.4 | c.4303A>G | p.Arg1435Gly | missense_variant | 34/35 | ENST00000423485.6 | |
TOP2A | XM_005257632.2 | c.4267A>G | p.Arg1423Gly | missense_variant | 34/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TOP2A | ENST00000423485.6 | c.4303A>G | p.Arg1435Gly | missense_variant | 34/35 | 1 | NM_001067.4 | P1 | |
TOP2A | ENST00000578412.1 | n.632A>G | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000697 AC: 17AN: 243976Hom.: 0 AF XY: 0.0000831 AC XY: 11AN XY: 132422
GnomAD4 exome AF: 0.000106 AC: 154AN: 1458172Hom.: 0 Cov.: 31 AF XY: 0.0000965 AC XY: 70AN XY: 725250
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.4303A>G (p.R1435G) alteration is located in exon 34 (coding exon 34) of the TOP2A gene. This alteration results from a A to G substitution at nucleotide position 4303, causing the arginine (R) at amino acid position 1435 to be replaced by a glycine (G). 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