rs790902

chr1-237793846-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.01

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]

ACMG classification

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	UniProt
RYR2	NM_001035.3	c.13783-21G>A		intron_variant		ENST00000366574.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99217 AN: 151782 Hom.: 33064 Cov.: 32

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

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.: 23 AF XY: 0.677 AC XY: 474626 AN XY: 700558

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.: 32 AF XY: 0.659 AC XY: 48914 AN XY: 74228

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Other links and lift over

dbSNP: rs790902; hg19: chr1-237957146;