rs397516545
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001035.3(RYR2):c.5754C>T(p.Val1918=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,532 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 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
RYR2
NM_001035.3 synonymous
NM_001035.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.106
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant 1-237617324-C-T is Benign according to our data. Variant chr1-237617324-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 43809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.106 with no splicing effect.
BS2
?
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.5754C>T | p.Val1918= | synonymous_variant | 38/105 | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.5754C>T | p.Val1918= | synonymous_variant | 38/105 | 1 | NM_001035.3 | P1 | |
RYR2 | ENST00000660292.2 | c.5754C>T | p.Val1918= | synonymous_variant | 38/106 | ||||
RYR2 | ENST00000659194.3 | c.5754C>T | p.Val1918= | synonymous_variant | 38/105 | ||||
RYR2 | ENST00000609119.2 | c.5754C>T | p.Val1918= | synonymous_variant, NMD_transcript_variant | 38/104 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000121 AC: 30AN: 248218Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 134654
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461350Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 726948
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GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74340
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
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 | Oct 06, 2011 | Val1918Val in exon 38 of RYR2: This variant does not change an amino acid and do es not affect the splice consensus sequence. This makes a disease causing role v ery unlikely. - |
Catecholaminergic polymorphic ventricular tachycardia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 01, 2021 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at