Variant rs2805396 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 NM_001035.3(RYR2):c.3424-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,551,862 control chromosomes in the GnomAD database, including 363,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 28394 hom., cov: 30)

Exomes 𝑓: 0.69 ( 335014 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.329

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:

RYR2 (HGNC:):

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=-0.84).

BP6

Variant 1-237569095-G-A is Benign according to our data. Variant chr1-237569095-G-A is described in ClinVar as [Benign]. Clinvar id is 257208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 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.3424-50G>A		intron_variant		ENST00000366574.7	NP_001026.2	Q92736-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.3424-50G>A	intron_variant	1	NM_001035.3	ENSP00000355533.2	Q92736-1
RYR2	ENST00000609119.2 linkuse as main transcript	n.3424-50G>A	intron_variant	5		ENSP00000499659.2	A0A590UK06
RYR2	ENST00000660292.2 linkuse as main transcript	c.3424-50G>A	intron_variant			ENSP00000499787.2	A0A590UKB7
RYR2	ENST00000659194.3 linkuse as main transcript	c.3424-50G>A	intron_variant			ENSP00000499653.3	A0A590UJZ8

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

88360

AN:

151684

Hom.:

28378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.839

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.656

Gnomad MID

AF:

0.628

Gnomad NFE

AF:

0.710

Gnomad OTH

AF:

0.610

GnomAD3 exomes

AF:

0.648

AC:

139415

AN:

215306

Hom.:

47621

AF XY:

0.656

AC XY:

75948

AN XY:

115768

show subpopulations

Gnomad AFR exome

AF:

0.307

Gnomad AMR exome

AF:

0.739

Gnomad ASJ exome

AF:

0.765

Gnomad EAS exome

AF:

0.264

Gnomad SAS exome

AF:

0.679

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.713

Gnomad OTH exome

AF:

0.686

GnomAD4 exome

AF:

0.685

AC:

959238

AN:

1400060

Hom.:

335014

Cov.:

AF XY:

0.687

AC XY:

474151

AN XY:

689832

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.738

Gnomad4 ASJ exome

AF:

0.777

Gnomad4 EAS exome

AF:

0.297

Gnomad4 SAS exome

AF:

0.685

Gnomad4 FIN exome

AF:

0.670

Gnomad4 NFE exome

AF:

0.709

Gnomad4 OTH exome

AF:

0.657

GnomAD4 genome

AF:

0.582

AC:

88408

AN:

151802

Hom.:

28394

Cov.:

AF XY:

0.581

AC XY:

43086

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.692

Gnomad4 ASJ

AF:

0.777

Gnomad4 EAS

AF:

0.275

Gnomad4 SAS

AF:

0.667

Gnomad4 FIN

AF:

0.656

Gnomad4 NFE

AF:

0.710

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.663

Hom.:

6481

Bravo

AF:

0.573

Asia WGS

AF:

0.474

AC:

1650

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.27

DANN

Benign

0.79

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