rs780707255
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_001035.3(RYR2):āc.6346A>Gā(p.Thr2116Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,974 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. T2116T) has been classified as Likely benign.
Frequency
Consequence
NM_001035.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.6346A>G | p.Thr2116Ala | missense_variant | 41/105 | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.6346A>G | p.Thr2116Ala | missense_variant | 41/105 | 1 | NM_001035.3 | P1 | |
RYR2 | ENST00000660292.2 | c.6346A>G | p.Thr2116Ala | missense_variant | 41/106 | ||||
RYR2 | ENST00000659194.3 | c.6346A>G | p.Thr2116Ala | missense_variant | 41/105 | ||||
RYR2 | ENST00000609119.2 | c.6346A>G | p.Thr2116Ala | missense_variant, NMD_transcript_variant | 41/104 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000602 AC: 15AN: 249114Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135156
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461704Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727134
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74450
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 20, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 16, 2023 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2021 | 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