GeneBe

rs2275693

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001035.3(RYR2):​c.14756+12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RYR2
NM_001035.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05

Publications

2 publications found
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 Gene-Disease associations (from GenCC):
  • arrhythmogenic right ventricular dysplasia 2
    Inheritance: AD Classification: DEFINITIVE, NO_KNOWN Submitted by: Laboratory for Molecular Medicine, Ambry Genetics
  • catecholaminergic polymorphic ventricular tachycardia
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P
  • catecholaminergic polymorphic ventricular tachycardia 1
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • hypertrophic cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • arrhythmogenic right ventricular cardiomyopathy
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 1-237830642-C-A is Benign according to our data. Variant chr1-237830642-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1541157.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RYR2NM_001035.3 linkc.14756+12C>A intron_variant Intron 103 of 104 ENST00000366574.7 NP_001026.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RYR2ENST00000366574.7 linkc.14756+12C>A intron_variant Intron 103 of 104 1 NM_001035.3 ENSP00000355533.2
RYR2ENST00000661330.2 linkc.14774+12C>A intron_variant Intron 104 of 105 ENSP00000499393.2
RYR2ENST00000609119.2 linkn.*5848+12C>A intron_variant Intron 102 of 103 5 ENSP00000499659.2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1289342
Hom.:
0
Cov.:
18
AF XY:
0.00
AC XY:
0
AN XY:
649556
African (AFR)
AF:
0.00
AC:
0
AN:
29886
American (AMR)
AF:
0.00
AC:
0
AN:
44026
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24754
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38618
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81912
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53190
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5446
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
956928
Other (OTH)
AF:
0.00
AC:
0
AN:
54582
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Oct 16, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.24
DANN
Benign
0.65
PhyloP100
-1.1

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

Other links and lift over

dbSNP: rs2275693; hg19: chr1-237993942; API