Variant 17-40400518-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001067.4(TOP2A):c.2799+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,601,858 control chromosomes in the GnomAD database, including 529,112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.85 ( 55111 hom., cov: 30)

Exomes 𝑓: 0.81 ( 474001 hom. )

Consequence

TOP2A
NM_001067.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Variant links:

Genes affected

TOP2A (HGNC:11989): (DNA topoisomerase II alpha) This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia. [provided by RefSeq, Jul 2010]

TOP2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TOP2A	NM_001067.4 link	c.2799+11A>G	intron_variant	ENST00000423485.6	NP_001058.2	P11388-1
TOP2A	XM_005257632.2 link	c.2763+11A>G	intron_variant		XP_005257689.1
TOP2A	XM_011525165.3 link	c.2799+11A>G	intron_variant		XP_011523467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOP2A	ENST00000423485.6 link	c.2799+11A>G		intron_variant		1	NM_001067.4	ENSP00000411532.1		P11388-1

Frequencies

GnomAD3 genomes

AF:

0.847

AC:

128717

AN:

152042

Hom.:

55047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.959

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.735

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.750

Gnomad SAS

AF:

0.691

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.819

Gnomad OTH

AF:

0.839

GnomAD3 exomes

AF:

0.788

AC:

186520

AN:

236714

Hom.:

74368

AF XY:

0.787

AC XY:

101276

AN XY:

128628

show subpopulations

Gnomad AFR exome

AF:

0.960

Gnomad AMR exome

AF:

0.633

Gnomad ASJ exome

AF:

0.838

Gnomad EAS exome

AF:

0.734

Gnomad SAS exome

AF:

0.707

Gnomad FIN exome

AF:

0.862

Gnomad NFE exome

AF:

0.819

Gnomad OTH exome

AF:

0.808

GnomAD4 exome

AF:

0.807

AC:

1169788

AN:

1449698

Hom.:

474001

Cov.:

AF XY:

0.804

AC XY:

579557

AN XY:

720710

show subpopulations

Gnomad4 AFR exome

AF:

0.965

Gnomad4 AMR exome

AF:

0.645

Gnomad4 ASJ exome

AF:

0.841

Gnomad4 EAS exome

AF:

0.737

Gnomad4 SAS exome

AF:

0.706

Gnomad4 FIN exome

AF:

0.857

Gnomad4 NFE exome

AF:

0.814

Gnomad4 OTH exome

AF:

0.820

GnomAD4 genome

AF:

0.847

AC:

128837

AN:

152160

Hom.:

55111

Cov.:

AF XY:

0.843

AC XY:

62703

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.959

Gnomad4 AMR

AF:

0.735

Gnomad4 ASJ

AF:

0.840

Gnomad4 EAS

AF:

0.749

Gnomad4 SAS

AF:

0.691

Gnomad4 FIN

AF:

0.866

Gnomad4 NFE

AF:

0.819

Gnomad4 OTH

AF:

0.841

Alfa

AF:

0.848

Hom.:

11845

Bravo

AF:

0.841

Asia WGS

AF:

0.780

AC:

2711

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over