rs762521873
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_001035.3(RYR2):c.8736G>A(p.Leu2912=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,458,954 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L2912L) has been classified as Likely benign.
Frequency
Consequence
NM_001035.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.8736G>A | p.Leu2912= | synonymous_variant | 60/105 | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.8736G>A | p.Leu2912= | synonymous_variant | 60/105 | 1 | NM_001035.3 | P1 | |
RYR2 | ENST00000660292.2 | c.8736G>A | p.Leu2912= | synonymous_variant | 60/106 | ||||
RYR2 | ENST00000659194.3 | c.8736G>A | p.Leu2912= | synonymous_variant | 60/105 | ||||
RYR2 | ENST00000609119.2 | c.8736G>A | p.Leu2912= | synonymous_variant, NMD_transcript_variant | 60/104 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248578Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134808
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1458954Hom.: 0 Cov.: 29 AF XY: 0.0000165 AC XY: 12AN XY: 725822
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cardiomyopathy Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 08, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 30, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 16, 2016 | p.Leu2912Leu in exon 60 of RYR2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 1/63490 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs762521873). - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 02, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at