1-237707259-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001035.3(RYR2):c.9891G>A(p.Lys3297Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,514,330 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
Consequence
NM_001035.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.9891G>A | p.Lys3297Lys | synonymous_variant | Exon 68 of 105 | 1 | NM_001035.3 | ENSP00000355533.2 | ||
RYR2 | ENST00000609119.2 | n.*926G>A | non_coding_transcript_exon_variant | Exon 66 of 104 | 5 | ENSP00000499659.2 | ||||
RYR2 | ENST00000609119.2 | n.*926G>A | 3_prime_UTR_variant | Exon 66 of 104 | 5 | ENSP00000499659.2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000254 AC: 5AN: 196888Hom.: 0 AF XY: 0.0000188 AC XY: 2AN XY: 106136
GnomAD4 exome AF: 0.0000139 AC: 19AN: 1362164Hom.: 0 Cov.: 26 AF XY: 0.0000135 AC XY: 9AN XY: 668624
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74328
ClinVar
Submissions by phenotype
not specified Benign:1
p.Lys3297Lys in exon 68 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 1/6608 European A merican chromosomes from a broad population by the NHLBI Exome Sequencing Projec t (http://evs.gs.washington.edu/EVS). -
Catecholaminergic polymorphic ventricular tachycardia Benign:1
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Cardiomyopathy Benign:1
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not provided Benign:1
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Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
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Cardiovascular phenotype Benign:1
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