Genetic Variant RUVBL2:p.Tyr215Tyr (chr19-49010048-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006666.3(RUVBL2):c.645C>T(p.Tyr215Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000478 in 1,599,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

RUVBL2
NM_006666.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.15

Publications

1 publications found

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:

MIR6798 (HGNC:50013): (microRNA 6798) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6798 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 19-49010048-C-T is Benign according to our data. Variant chr19-49010048-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650228.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.15 with no splicing effect.

BS2

High AC in GnomAd4 at 77 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006666.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUVBL2	NM_006666.3	MANE Select	c.645C>T	p.Tyr215Tyr	synonymous	Exon 8 of 15	NP_006657.1	Q9Y230-1
RUVBL2	NM_001321190.2		c.543C>T	p.Tyr181Tyr	synonymous	Exon 8 of 15	NP_001308119.1	B3KNL2
RUVBL2	NM_001321191.1		c.510C>T	p.Tyr170Tyr	synonymous	Exon 8 of 15	NP_001308120.1	Q9Y230-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUVBL2	ENST00000595090.6	TSL:1 MANE Select	c.645C>T	p.Tyr215Tyr	synonymous	Exon 8 of 15	ENSP00000473172.1	Q9Y230-1
RUVBL2	ENST00000221413.10	TSL:1	n.634C>T		non_coding_transcript_exon	Exon 8 of 15	ENSP00000221413.6	X6R2L4
RUVBL2	ENST00000888169.1		c.666C>T	p.Tyr222Tyr	synonymous	Exon 8 of 15	ENSP00000558228.1

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000438

AC:

103

AN:

235326

AF XY:

0.000453

show subpopulations

Gnomad AFR exome

AF:

0.000197

Gnomad AMR exome

AF:

0.0000619

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.0000569

Gnomad FIN exome

AF:

0.000195

Gnomad NFE exome

AF:

0.000812

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.000475

AC:

687

AN:

1447024

Hom.:

Cov.:

AF XY:

0.000508

AC XY:

365

AN XY:

719166

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

32978

American (AMR)

AF:

0.0000703

AC:

AN:

42678

Ashkenazi Jewish (ASJ)

AF:

0.0000806

AC:

AN:

24822

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39604

South Asian (SAS)

AF:

0.0000830

AC:

AN:

84346

European-Finnish (FIN)

AF:

0.000249

AC:

AN:

52234

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.000581

AC:

642

AN:

1105058

Other (OTH)

AF:

0.000218

AC:

AN:

59644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000506

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000970

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000743

Hom.:

Bravo

AF:

0.000423

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.19

(source)

DANN

Benign

0.64

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over