Variant rs790902 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.13783-21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,557,336 control chromosomes in the GnomAD database, including 356,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33082 hom., cov: 32)

Exomes 𝑓: 0.67 ( 322922 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.01

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=-0.91).

BP6

Variant 1-237793846-G-A is Benign according to our data. Variant chr1-237793846-G-A is described in ClinVar as [Benign]. Clinvar id is 257201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237793846-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 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.13783-21G>A		intron_variant		ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.13783-21G>A		intron_variant		1	NM_001035.3	ENSP00000355533	P1	Q92736-1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99217

AN:

151782

Hom.:

33064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.831

Gnomad AMR

AF:

0.735

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.949

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.664

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.662

Gnomad OTH

AF:

0.635

GnomAD3 exomes

AF:

0.711

AC:

164552

AN:

231294

Hom.:

59876

AF XY:

0.711

AC XY:

88801

AN XY:

124818

show subpopulations

Gnomad AFR exome

AF:

0.542

Gnomad AMR exome

AF:

0.812

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.942

Gnomad SAS exome

AF:

0.823

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.686

GnomAD4 exome

AF:

0.673

AC:

945971

AN:

1405436

Hom.:

322922

Cov.:

AF XY:

0.677

AC XY:

474626

AN XY:

700558

show subpopulations

Gnomad4 AFR exome

AF:

0.536

Gnomad4 AMR exome

AF:

0.805

Gnomad4 ASJ exome

AF:

0.619

Gnomad4 EAS exome

AF:

0.935

Gnomad4 SAS exome

AF:

0.821

Gnomad4 FIN exome

AF:

0.677

Gnomad4 NFE exome

AF:

0.652

Gnomad4 OTH exome

AF:

0.671

GnomAD4 genome

AF:

0.654

AC:

99277

AN:

151900

Hom.:

33082

Cov.:

AF XY:

0.659

AC XY:

48914

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.550

Gnomad4 AMR

AF:

0.735

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.949

Gnomad4 SAS

AF:

0.825

Gnomad4 FIN

AF:

0.664

Gnomad4 NFE

AF:

0.662

Gnomad4 OTH

AF:

0.639

Alfa

AF:

0.613

Hom.:

3873

Bravo

AF:

0.653

Asia WGS

AF:

0.856

AC:

2972

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Arrhythmogenic right ventricular dysplasia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Cardiac arrhythmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.024

DANN

Benign

0.67

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