rs750047302
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2
The NM_001035.3(RYR2):c.294+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,605,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
RYR2
NM_001035.3 intron
NM_001035.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.80
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.18).
BP6
Variant 1-237356000-G-A is Benign according to our data. Variant chr1-237356000-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.294+15G>A | intron_variant | ENST00000366574.7 | NP_001026.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.294+15G>A | intron_variant | 1 | NM_001035.3 | ENSP00000355533.2 | ||||
RYR2 | ENST00000609119.2 | n.294+15G>A | intron_variant | 5 | ENSP00000499659.2 | |||||
RYR2 | ENST00000660292.2 | c.294+15G>A | intron_variant | ENSP00000499787.2 | ||||||
RYR2 | ENST00000659194.3 | c.294+15G>A | intron_variant | ENSP00000499653.3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152028Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
5
AN:
152028
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000253 AC: 6AN: 236778Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 127804
GnomAD3 exomes
AF:
AC:
6
AN:
236778
Hom.:
AF XY:
AC XY:
2
AN XY:
127804
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000121 AC: 176AN: 1453040Hom.: 0 Cov.: 30 AF XY: 0.000107 AC XY: 77AN XY: 722014
GnomAD4 exome
AF:
AC:
176
AN:
1453040
Hom.:
Cov.:
30
AF XY:
AC XY:
77
AN XY:
722014
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152028Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74244
GnomAD4 genome
AF:
AC:
5
AN:
152028
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74244
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 07, 2015 | c.294+15G>A in intron 4 of RYR2: This variant is not expected to have clinical s ignificance because it is not located within the splice consensus sequence. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at