Variant rs16835818 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.13476+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,449,050 control chromosomes in the GnomAD database, including 66,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9830 hom., cov: 32)

Exomes 𝑓: 0.29 ( 56197 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.598

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=-0.92).

BP6

Variant 1-237788182-G-A is Benign according to our data. Variant chr1-237788182-G-A is described in ClinVar as [Benign]. Clinvar id is 257200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3 linkuse as main transcript	c.13476+47G>A		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.13476+47G>A	intron_variant	1	NM_001035.3	P1	Q92736-1
RYR2	ENST00000659194.3 linkuse as main transcript	c.13458+47G>A	intron_variant
RYR2	ENST00000660292.2 linkuse as main transcript	c.13497+47G>A	intron_variant
RYR2	ENST00000609119.2 linkuse as main transcript	c.*4568+47G>A	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51381

AN:

151976

Hom.:

9808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.299

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.267

AC:

49709

AN:

185982

Hom.:

7190

AF XY:

0.269

AC XY:

26652

AN XY:

99160

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.272

GnomAD4 exome

AF:

0.288

AC:

373606

AN:

1296954

Hom.:

56197

Cov.:

AF XY:

0.287

AC XY:

183848

AN XY:

641316

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.338

AC:

51439

AN:

152096

Hom.:

9830

Cov.:

AF XY:

0.331

AC XY:

24626

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.296

Gnomad4 OTH

AF:

0.307

Alfa

AF:

0.304

Hom.:

8056

Bravo

AF:

0.345

Asia WGS

AF:

0.184

AC:

641

AN:

3478

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	Jun 18, 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

- -

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

-0.92

CADD

Benign

0.0020

DANN

Benign

0.68

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