rs750384592
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001035.3(RYR2):c.11208G>A(p.Ala3736=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,298 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A3736A) 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 -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.11208G>A | p.Ala3736= | synonymous_variant | 81/105 | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.11208G>A | p.Ala3736= | synonymous_variant | 81/105 | 1 | NM_001035.3 | P1 | |
RYR2 | ENST00000660292.2 | c.11196G>A | p.Ala3732= | synonymous_variant | 81/106 | ||||
RYR2 | ENST00000659194.3 | c.11196G>A | p.Ala3732= | synonymous_variant | 81/105 | ||||
RYR2 | ENST00000609119.2 | c.*2300G>A | 3_prime_UTR_variant, NMD_transcript_variant | 80/104 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248498Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134804
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461156Hom.: 1 Cov.: 30 AF XY: 0.0000275 AC XY: 20AN XY: 726870
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
Cardiomyopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jun 18, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 10, 2018 | - - |
Catecholaminergic polymorphic ventricular tachycardia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 13, 2023 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 15, 2019 | 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