19-49004325-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006666.3(RUVBL2):​c.172G>A​(p.Val58Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,611,056 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RUVBL2
NM_006666.3 missense

Scores

2
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

Publications

0 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39887345).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RUVBL2NM_006666.3 linkc.172G>A p.Val58Met missense_variant Exon 4 of 15 ENST00000595090.6 NP_006657.1 Q9Y230-1
RUVBL2NM_001321190.2 linkc.70G>A p.Val24Met missense_variant Exon 4 of 15 NP_001308119.1 B3KNL2
RUVBL2NM_001321191.1 linkc.37G>A p.Val13Met missense_variant Exon 4 of 15 NP_001308120.1 Q9Y230-2
RUVBL2NR_135578.2 linkn.197G>A non_coding_transcript_exon_variant Exon 4 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RUVBL2ENST00000595090.6 linkc.172G>A p.Val58Met missense_variant Exon 4 of 15 1 NM_006666.3 ENSP00000473172.1 Q9Y230-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151986
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000407
AC:
1
AN:
245488
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000558
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1459070
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726026
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33462
American (AMR)
AF:
0.00
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39696
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86216
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51258
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5462
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111820
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60318
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000658
AC:
1
AN:
151986
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74224
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41394
American (AMR)
AF:
0.00
AC:
0
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5170
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10578
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67968
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.172G>A (p.V58M) alteration is located in exon 4 (coding exon 4) of the RUVBL2 gene. This alteration results from a G to A substitution at nucleotide position 172, causing the valine (V) at amino acid position 58 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.38
T;T;T;T
Eigen
Benign
0.13
Eigen_PC
Benign
0.042
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.99
D;.;D;D
M_CAP
Uncertain
0.091
D
MetaRNN
Benign
0.40
T;T;T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.9
L;.;.;.
PhyloP100
3.7
PrimateAI
Pathogenic
0.80
T
Sift4G
Benign
0.077
T;T;T;T
Polyphen
1.0
D;.;.;.
Vest4
0.43
MutPred
0.45
Loss of catalytic residue at V58 (P = 0.0055);.;.;.;
MVP
0.67
MPC
2.0
ClinPred
0.83
D
GERP RS
3.7
PromoterAI
0.0074
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.79
Mutation Taster
=69/31
polymorphism

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

Other links and lift over

dbSNP: rs1425514806; hg19: chr19-49507582; API