Variant chr19-49010042-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.639C>T(p.Arg213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,597,190 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 14 hom. )

Consequence

RUVBL2
NM_006666.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -8.16

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=-0.81).

BP6

Variant 19-49010042-C-T is Benign according to our data. Variant chr19-49010042-C-T is described in ClinVar as [Benign]. Clinvar id is 781514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.16 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00605 (922/152300) while in subpopulation AFR AF= 0.0213 (887/41558). AF 95% confidence interval is 0.0202. There are 16 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 922 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RUVBL2	NM_006666.3 linkuse as main transcript	c.639C>T	p.Arg213=	synonymous_variant	8/15	ENST00000595090.6
RUVBL2	NM_001321190.2 linkuse as main transcript	c.537C>T	p.Arg179=	synonymous_variant	8/15
RUVBL2	NM_001321191.1 linkuse as main transcript	c.504C>T	p.Arg168=	synonymous_variant	8/15
RUVBL2	NR_135578.2 linkuse as main transcript	n.653C>T		non_coding_transcript_exon_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUVBL2	ENST00000595090.6 linkuse as main transcript	c.639C>T	p.Arg213=	synonymous_variant	8/15	1	NM_006666.3	P1	Q9Y230-1

Frequencies

GnomAD3 genomes

AF:

0.00606

AC:

922

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00154

AC:

361

AN:

234028

Hom.:

AF XY:

0.00113

AC XY:

144

AN XY:

127076

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.000620

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000569

Gnomad SAS exome

AF:

0.000214

Gnomad FIN exome

AF:

0.0000979

Gnomad NFE exome

AF:

0.0000563

Gnomad OTH exome

AF:

0.000720

GnomAD4 exome

AF:

0.000638

AC:

922

AN:

1444890

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

384

AN XY:

717734

show subpopulations

Gnomad4 AFR exome

AF:

0.0220

Gnomad4 AMR exome

AF:

0.000775

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000214

Gnomad4 FIN exome

AF:

0.000325

Gnomad4 NFE exome

AF:

0.0000553

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00605

AC:

922

AN:

152300

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

424

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.00683

Asia WGS

AF:

0.00115

AC:

AN:

3478

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.12

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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