Variant 19-49011063-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006666.3(RUVBL2):c.852C>T(p.Arg284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000811 in 1,608,224 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 6 hom. )

Consequence

RUVBL2
NM_006666.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.96

Variant links:

Genes affected

RUVBL2 (HGNC:10475): (RuvB like AAA ATPase 2) This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helicase essential for homologous recombination and DNA double-strand break repair. Functional analysis showed that this gene product has both ATPase and DNA helicase activities. This gene is physically linked to the CGB/LHB gene cluster on chromosome 19q13.3, and is very close (55 nt) to the LHB gene, in the opposite orientation. [provided by RefSeq, Jul 2008]

RUVBL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 19-49011063-C-T is Benign according to our data. Variant chr19-49011063-C-T is described in ClinVar as [Benign]. Clinvar id is 709500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.96 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00463 (692/149388) while in subpopulation AFR AF= 0.0165 (670/40712). AF 95% confidence interval is 0.0154. There are 6 homozygotes in gnomad4. There are 332 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 692 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RUVBL2	NM_006666.3 linkuse as main transcript	c.852C>T	p.Arg284=	synonymous_variant	10/15	ENST00000595090.6	NP_006657.1
RUVBL2	NM_001321190.2 linkuse as main transcript	c.750C>T	p.Arg250=	synonymous_variant	10/15		NP_001308119.1
RUVBL2	NM_001321191.1 linkuse as main transcript	c.717C>T	p.Arg239=	synonymous_variant	10/15		NP_001308120.1
RUVBL2	NR_135578.2 linkuse as main transcript	n.866C>T		non_coding_transcript_exon_variant	10/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUVBL2	ENST00000595090.6 linkuse as main transcript	c.852C>T	p.Arg284=	synonymous_variant	10/15	1	NM_006666.3	ENSP00000473172	P1	Q9Y230-1

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

684

AN:

149282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000801

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000609

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00108

AC:

267

AN:

246530

Hom.:

AF XY:

0.000859

AC XY:

115

AN XY:

133850

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.000698

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000727

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000420

AC:

612

AN:

1458836

Hom.:

Cov.:

AF XY:

0.000379

AC XY:

275

AN XY:

725590

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.000717

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000379

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.000830

GnomAD4 genome

AF:

0.00463

AC:

692

AN:

149388

Hom.:

Cov.:

AF XY:

0.00456

AC XY:

332

AN XY:

72842

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.000800

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000610

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00503

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.2

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over