rs373112536
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001035.3(RYR2):c.6166+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,612,600 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001035.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.6166+8G>A | splice_region_variant, intron_variant | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.6166+8G>A | splice_region_variant, intron_variant | 1 | NM_001035.3 | P1 | |||
RYR2 | ENST00000659194.3 | c.6166+8G>A | splice_region_variant, intron_variant | ||||||
RYR2 | ENST00000660292.2 | c.6166+8G>A | splice_region_variant, intron_variant | ||||||
RYR2 | ENST00000609119.2 | c.6166+8G>A | splice_region_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000405 AC: 10AN: 246994Hom.: 1 AF XY: 0.0000746 AC XY: 10AN XY: 134034
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1460446Hom.: 1 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 726438
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74320
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | 6616+8G>A in intron 40 of RYR2: This variant is not expected to have clinical si gnificance because it is not located within the conserved region of the splice c onsensus sequence. 6616+8G>A in intron 40 of RYR2 (allele frequency = n/a) - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at