RUVBL2 p.Leu205Leu

Variant names:

• chr19-49010015-G-G
• ENST00000595090.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-49010016--
• chr19-49010016-C-T
• chr19-49010018-G-T
• chr19-49010018-G-C
• chr19-49010018-G-A
• chr19-49010016-CTG-TTA

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The ENST00000595090.6(RUVBL2):​c. variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUVBL2 ENST00000595090.6 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000595090.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR6798	NR_106856.1		n.		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL2	ENST00000595090.6	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000473172.1	Q9Y230-1
	RUVBL2	ENST00000221413.10	TSL:1	n.		splice_donor intron	N/A	ENSP00000221413.6	X6R2L4
	RUVBL2	ENST00000888169.1		c.		splice_donor intron	N/A	ENSP00000558228.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-49513272;