rs775418111
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_001035.3(RYR2):c.13782+10_13782+13del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 1,587,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000060 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
RYR2
NM_001035.3 splice_region, intron
NM_001035.3 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.990
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
?
Variant 1-237792330-TAGTA-T is Benign according to our data. Variant chr1-237792330-TAGTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 463569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.13782+10_13782+13del | splice_region_variant, intron_variant | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.13782+10_13782+13del | splice_region_variant, intron_variant | 1 | NM_001035.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000603 AC: 9AN: 149134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000338 AC: 8AN: 236384Hom.: 0 AF XY: 0.0000310 AC XY: 4AN XY: 129018
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GnomAD4 exome AF: 0.0000160 AC: 23AN: 1437902Hom.: 0 AF XY: 0.0000154 AC XY: 11AN XY: 714368
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GnomAD4 genome ? AF: 0.0000603 AC: 9AN: 149250Hom.: 0 Cov.: 32 AF XY: 0.0000965 AC XY: 7AN XY: 72528
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2017 | 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. - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2023 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at