GeneBe

rs35563566

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001035.3(RYR2):​c.14091-15_14091-11delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000821 in 1,218,062 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RYR2NM_001035.3 linkc.14091-15_14091-11delTTTTT intron_variant Intron 97 of 104 ENST00000366574.7 NP_001026.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RYR2ENST00000366574.7 linkc.14091-22_14091-18delTTTTT intron_variant Intron 97 of 104 1 NM_001035.3 ENSP00000355533.2
RYR2ENST00000661330.2 linkc.14109-22_14109-18delTTTTT intron_variant Intron 98 of 105 ENSP00000499393.2
RYR2ENST00000609119.2 linkn.*5183-22_*5183-18delTTTTT intron_variant Intron 96 of 103 5 ENSP00000499659.2

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
8.21e-7
AC:
1
AN:
1218062
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
608294
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
28128
American (AMR)
AF:
0.00
AC:
0
AN:
38822
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22690
East Asian (EAS)
AF:
0.0000276
AC:
1
AN:
36188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
72842
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40786
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4992
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
922338
Other (OTH)
AF:
0.00
AC:
0
AN:
51276
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs35563566; hg19: chr1-237965133; API