19-49010600-CG-TC

Variant names:

• chr19-49010600-CG-TC
• NM_006666.3:c.776_777delCGinsTC
• RUVBL2 p.Ala259Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006666.3(RUVBL2):​c.776_777delCGinsTC​(p.Ala259Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RUVBL2 NM_006666.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.31
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL2	NM_006666.3	MANE Select	c.776_777delCGinsTC	p.Ala259Val	missense	N/A	NP_006657.1	Q9Y230-1
	RUVBL2	NM_001321190.2		c.674_675delCGinsTC	p.Ala225Val	missense	N/A	NP_001308119.1	B3KNL2
	RUVBL2	NM_001321191.1		c.641_642delCGinsTC	p.Ala214Val	missense	N/A	NP_001308120.1	Q9Y230-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUVBL2	ENST00000595090.6	TSL:1 MANE Select	c.776_777delCGinsTC	p.Ala259Val	missense	N/A	ENSP00000473172.1	Q9Y230-1
	RUVBL2	ENST00000221413.10	TSL:1	n.765_766delCGinsTC		non_coding_transcript_exon	Exon 9 of 15	ENSP00000221413.6	X6R2L4
	RUVBL2	ENST00000888169.1		c.797_798delCGinsTC	p.Ala266Val	missense	N/A	ENSP00000558228.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3

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: chr19-49513857;