rs750815004
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate
The NM_001035.3(RYR2):c.2029T>A(p.Leu677Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L677V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001035.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.2029T>A | p.Leu677Met | missense_variant | 20/105 | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.2029T>A | p.Leu677Met | missense_variant | 20/105 | 1 | NM_001035.3 | P1 | |
RYR2 | ENST00000660292.2 | c.2029T>A | p.Leu677Met | missense_variant | 20/106 | ||||
RYR2 | ENST00000659194.3 | c.2029T>A | p.Leu677Met | missense_variant | 20/105 | ||||
RYR2 | ENST00000609119.2 | c.2029T>A | p.Leu677Met | missense_variant, NMD_transcript_variant | 20/104 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249282Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135242
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727136
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at