rs7624894

Positions:

• chr3-25600666-T-C
• chr3-25600666-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330700.2(TOP2B):​c.4615+434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,168 control chromosomes in the GnomAD database, including 4,980 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 0.20 (4980 hom., cov: 32)
• Consequence: TOP2B NM_001330700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

Genes affected

TOP2B (HGNC:11990): (DNA topoisomerase II beta) 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, beta, is localized to chromosome 3 and the alpha form is localized to chromosome 17. 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOP2B	NM_001330700.2	c.4615+434A>G		intron_variant		ENST00000264331.9	NP_001317629.1
TOP2B	NM_001068.3	c.4600+434A>G		intron_variant			NP_001059.2
TOP2B	XM_011534057.4	c.4504+434A>G		intron_variant			XP_011532359.1
TOP2B	XM_047448821.1	c.4489+434A>G		intron_variant			XP_047304777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOP2B	ENST00000264331.9	c.4615+434A>G		intron_variant		5	NM_001330700.2	ENSP00000264331	A2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30892 AN: 152050 Hom.: 4963 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.203 AC: 30951 AN: 152168 Hom.: 4980 Cov.: 32 AF XY: 0.200 AC XY: 14911 AN XY: 74408

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0995

Gnomad4 NFE AF: 0.0945

Gnomad4 OTH AF: 0.173

Alfa AF: 0.0780 Hom.: 191

Bravo AF: 0.221

Asia WGS AF: 0.159 AC: 552 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs7624894; hg19: chr3-25642157;