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GeneBe

19-49010042-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-8.16 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 922 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RUVBL2NM_006666.3 linkuse as main transcriptc.639C>T p.Arg213= synonymous_variant 8/15 ENST00000595090.6
RUVBL2NM_001321190.2 linkuse as main transcriptc.537C>T p.Arg179= synonymous_variant 8/15
RUVBL2NM_001321191.1 linkuse as main transcriptc.504C>T p.Arg168= synonymous_variant 8/15
RUVBL2NR_135578.2 linkuse as main transcriptn.653C>T non_coding_transcript_exon_variant 8/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RUVBL2ENST00000595090.6 linkuse as main transcriptc.639C>T p.Arg213= synonymous_variant 8/151 NM_006666.3 P1Q9Y230-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00606
AC:
922
AN:
152182
Hom.:
16
Cov.:
33
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.:
8
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.:
14
Cov.:
37
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00605
AC:
922
AN:
152300
Hom.:
16
Cov.:
33
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.:
5
Bravo
AF:
0.00683
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 08, 2018- -

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.

Other links and lift over

dbSNP: rs145890647; hg19: chr19-49513299; API