19-49010016-C-T

Variant names:

• chr19-49010016-C-T
• rs1062708
• NM_006666.3:c.613C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006666.3(RUVBL2):​c.613C>T​(p.Leu205Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,589,768 control chromosomes in the GnomAD database, including 181,568 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (14424 hom., cov: 32)
  • Exomes 𝑓: 0.48 (167144 hom.)
• Consequence: RUVBL2 NM_006666.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 34 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=2.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

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.613C>T	p.Leu205Leu	synonymous	Exon 8 of 15	NP_006657.1	Q9Y230-1
	RUVBL2	NM_001321190.2		c.511C>T	p.Leu171Leu	synonymous	Exon 8 of 15	NP_001308119.1	B3KNL2
	RUVBL2	NM_001321191.1		c.478C>T	p.Leu160Leu	synonymous	Exon 8 of 15	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.613C>T	p.Leu205Leu	synonymous	Exon 8 of 15	ENSP00000473172.1	Q9Y230-1
	RUVBL2	ENST00000221413.10	TSL:1	n.602C>T		non_coding_transcript_exon	Exon 8 of 15	ENSP00000221413.6	X6R2L4
	RUVBL2	ENST00000888169.1		c.634C>T	p.Leu212Leu	synonymous	Exon 8 of 15	ENSP00000558228.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63719 AN: 151904 Hom.: 14422 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.419

GnomAD2 exomes AF: 0.480 AC: 112028 AN: 233248 AF XY: 0.483

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.563

Gnomad EAS exome AF: 0.402

Gnomad FIN exome AF: 0.474

Gnomad NFE exome AF: 0.493

Gnomad OTH exome AF: 0.482

GnomAD4 exome AF: 0.479 AC: 689091 AN: 1437744 Hom.: 167144 Cov.: 52 AF XY: 0.480 AC XY: 341952 AN XY: 712516

African (AFR) AF: 0.237 AC: 7820 AN: 32932

American (AMR) AF: 0.567 AC: 24281 AN: 42836

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 13634 AN: 24422

East Asian (EAS) AF: 0.426 AC: 16799 AN: 39438

South Asian (SAS) AF: 0.470 AC: 39029 AN: 83020

European-Finnish (FIN) AF: 0.472 AC: 24682 AN: 52288

Middle Eastern (MID) AF: 0.521 AC: 2934 AN: 5630

European-Non Finnish (NFE) AF: 0.485 AC: 532236 AN: 1097970

Other (OTH) AF: 0.467 AC: 27676 AN: 59208

GnomAD4 genome AF: 0.419 AC: 63722 AN: 152024 Hom.: 14424 Cov.: 32 AF XY: 0.420 AC XY: 31236 AN XY: 74330

African (AFR) AF: 0.242 AC: 10041 AN: 41484

American (AMR) AF: 0.478 AC: 7309 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1884 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2128 AN: 5164

South Asian (SAS) AF: 0.467 AC: 2253 AN: 4820

European-Finnish (FIN) AF: 0.469 AC: 4958 AN: 10578

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33601 AN: 67924

Other (OTH) AF: 0.416 AC: 877 AN: 2108

Alfa AF: 0.463 Hom.: 40707

Bravo AF: 0.411

Asia WGS AF: 0.371 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.37
CADD	Benign	10
DANN	Benign	0.86
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1062708; hg19: chr19-49513273; COSMIC: COSV55485346; COSMIC: COSV55485346;