19-49010048-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006666.3(RUVBL2):c.645C>T(p.Tyr215=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 GnomAd at 78 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUVBL2	NM_006666.3	c.645C>T	p.Tyr215=	synonymous_variant	8/15	ENST00000595090.6
RUVBL2	NM_001321190.2	c.543C>T	p.Tyr181=	synonymous_variant	8/15
RUVBL2	NM_001321191.1	c.510C>T	p.Tyr170=	synonymous_variant	8/15
RUVBL2	NR_135578.2	n.659C>T		non_coding_transcript_exon_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUVBL2	ENST00000595090.6	c.645C>T	p.Tyr215=	synonymous_variant	8/15	1	NM_006666.3	P1

Frequencies

GnomAD3 genomes AF: 0.000513 AC: 78 AN: 152194 Hom.: 0 Cov.: 33

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

GnomAD3 exomes AF: 0.000438 AC: 103 AN: 235326 Hom.: 0 AF XY: 0.000453 AC XY: 58 AN XY: 128008

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 SAS exome AF: 0.000141

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.: 0 Cov.: 37 AF XY: 0.000508 AC XY: 365 AN XY: 719166

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.0000703

Gnomad4 ASJ exome AF: 0.0000806

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.0000830

Gnomad4 FIN exome AF: 0.000249

Gnomad4 NFE exome AF: 0.000581

Gnomad4 OTH exome AF: 0.000218

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.000483 AC XY: 36 AN XY: 74476

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000970

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000743 Hom.: 0

Bravo AF: 0.000423

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

RUVBL2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	0.19
Dann	Benign	0.64
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

Other links and lift over

dbSNP: rs138614683; hg19: chr19-49513305;