19-49015801-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006666.3(RUVBL2):c.1367-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,613,232 control chromosomes in the GnomAD database, including 280,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (30424 hom., cov: 32)
  • Exomes 𝑓: 0.58 (249935 hom.)
• Consequence: RUVBL2 NM_006666.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0660

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-49015801-T-C is Benign according to our data. Variant chr19-49015801-T-C is described in ClinVar as [Benign]. Clinvar id is 1277510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUVBL2	NM_006666.3	c.1367-16T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000595090.6
RUVBL2	NM_001321190.2	c.1265-16T>C		splice_polypyrimidine_tract_variant, intron_variant
RUVBL2	NM_001321191.1	c.1232-16T>C		splice_polypyrimidine_tract_variant, intron_variant
RUVBL2	NR_135578.2	n.1381-16T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUVBL2	ENST00000595090.6	c.1367-16T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006666.3	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95252 AN: 151970 Hom.: 30392 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.597

GnomAD3 exomes AF: 0.592 AC: 147970 AN: 249866 Hom.: 45050 AF XY: 0.585 AC XY: 79236 AN XY: 135544

Gnomad AFR exome AF: 0.727

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.566

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.548

Gnomad FIN exome AF: 0.627

Gnomad NFE exome AF: 0.590

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.582 AC: 849875 AN: 1461144 Hom.: 249935 Cov.: 50 AF XY: 0.580 AC XY: 421754 AN XY: 726920

Gnomad4 AFR exome AF: 0.735

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.627 AC: 95330 AN: 152088 Hom.: 30424 Cov.: 32 AF XY: 0.626 AC XY: 46539 AN XY: 74328

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.594

Alfa AF: 0.621 Hom.: 3500

Bravo AF: 0.629

Asia WGS AF: 0.449 AC: 1565 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	11
Dann	Benign	0.72

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: rs749776; hg19: chr19-49519058; COSMIC: COSV55484610; COSMIC: COSV55484610;