NM_006666.3:c.5C>A

Variant names:

• chr19-48993916-C-A
• rs755510150
• NM_006666.3:c.5C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_006666.3(RUVBL2):​c.5C>A​(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RUVBL2 NM_006666.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• 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 3 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity RUVB2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34385002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUVBL2	NM_006666.3	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 15	ENST00000595090.6	NP_006657.1
RUVBL2	NR_135578.2	n.30C>A		non_coding_transcript_exon_variant	Exon 1 of 15
RUVBL2	NM_001321190.2	c.-168C>A		5_prime_UTR_variant	Exon 1 of 15		NP_001308119.1
RUVBL2	NM_001321191.1	c.-124+14C>A		intron_variant	Intron 1 of 14		NP_001308120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUVBL2	ENST00000595090.6	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 15	1	NM_006666.3	ENSP00000473172.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.2
PrimateAI	Pathogenic	0.80	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.046	B
Vest4		0.43
MutPred		0.11		Gain of disorder (P = 0.0745);
MVP		0.54
MPC		1.1
ClinPred		0.95	D
GERP RS		4.1
PromoterAI		-0.0022	Neutral
Varity_R		0.50
gMVP		0.83
Mutation Taster		=261/39	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

Other links and lift over

dbSNP: rs755510150; hg19: chr19-49497173;