Variant rs80013027 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000366574.7(RYR2):c.11776-21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 1,332,970 control chromosomes in the GnomAD database, including 1,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 165 hom., cov: 33)

Exomes 𝑓: 0.048 ( 1519 hom. )

Consequence

RYR2
ENST00000366574.7 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.14

Variant links:

Genes affected

RYR2 (HGNC:10484): (ryanodine receptor 2) This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]

RYR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-237778645-G-A is Benign according to our data. Variant chr1-237778645-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237778645-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3 linkuse as main transcript	c.11776-21G>A		intron_variant		ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.11776-21G>A	intron_variant	1	NM_001035.3	ENSP00000355533	P1	Q92736-1
RYR2	ENST00000659194.3 linkuse as main transcript	c.11764-21G>A	intron_variant			ENSP00000499653
RYR2	ENST00000660292.2 linkuse as main transcript	c.11797-21G>A	intron_variant			ENSP00000499787
RYR2	ENST00000609119.2 linkuse as main transcript	c.*2868-21G>A	intron_variant, NMD_transcript_variant	5		ENSP00000499659

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6731

AN:

152046

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.0612

Gnomad SAS

AF:

0.0512

Gnomad FIN

AF:

0.0704

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0484

Gnomad OTH

AF:

0.0450

GnomAD3 exomes

AF:

0.0449

AC:

10346

AN:

230516

Hom.:

297

AF XY:

0.0456

AC XY:

5715

AN XY:

125320

show subpopulations

Gnomad AFR exome

AF:

0.0297

Gnomad AMR exome

AF:

0.0200

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.0669

Gnomad SAS exome

AF:

0.0551

Gnomad FIN exome

AF:

0.0701

Gnomad NFE exome

AF:

0.0451

Gnomad OTH exome

AF:

0.0422

GnomAD4 exome

AF:

0.0477

AC:

56319

AN:

1180806

Hom.:

1519

Cov.:

AF XY:

0.0476

AC XY:

28249

AN XY:

592940

show subpopulations

Gnomad4 AFR exome

AF:

0.0286

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.0672

Gnomad4 SAS exome

AF:

0.0512

Gnomad4 FIN exome

AF:

0.0661

Gnomad4 NFE exome

AF:

0.0484

Gnomad4 OTH exome

AF:

0.0449

GnomAD4 genome

AF:

0.0442

AC:

6725

AN:

152164

Hom.:

165

Cov.:

AF XY:

0.0457

AC XY:

3401

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.0372

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.0608

Gnomad4 SAS

AF:

0.0498

Gnomad4 FIN

AF:

0.0704

Gnomad4 NFE

AF:

0.0485

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0429

Hom.:

Bravo

AF:

0.0405

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.12

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over