Variant chr1-237633537-G-A 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.6556-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,610,230 control chromosomes in the GnomAD database, including 102,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12271 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90720 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.235

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 1-237633537-G-A is Benign according to our data. Variant chr1-237633537-G-A is described in ClinVar as [Benign]. Clinvar id is 257214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 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.6556-41G>A		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.6556-41G>A	intron_variant	1	NM_001035.3	P1	Q92736-1
RYR2	ENST00000659194.3 linkuse as main transcript	c.6556-41G>A	intron_variant
RYR2	ENST00000660292.2 linkuse as main transcript	c.6556-41G>A	intron_variant
RYR2	ENST00000609119.2 linkuse as main transcript	c.6556-41G>A	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59993

AN:

151868

Hom.:

12238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.362

AC:

89803

AN:

248406

Hom.:

16810

AF XY:

0.356

AC XY:

48001

AN XY:

134812

show subpopulations

Gnomad AFR exome

AF:

0.513

Gnomad AMR exome

AF:

0.391

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.465

Gnomad SAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.336

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.350

AC:

509664

AN:

1458244

Hom.:

90720

Cov.:

AF XY:

0.349

AC XY:

252758

AN XY:

725216

show subpopulations

Gnomad4 AFR exome

AF:

0.507

Gnomad4 AMR exome

AF:

0.396

Gnomad4 ASJ exome

AF:

0.210

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.349

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.343

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.395

AC:

60080

AN:

151986

Hom.:

12271

Cov.:

AF XY:

0.393

AC XY:

29220

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.505

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.373

Alfa

AF:

0.342

Hom.:

11269

Bravo

AF:

0.405

Asia WGS

AF:

0.457

AC:

1588

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 16, 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

1.8

DANN

Benign

0.55

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