chr1-237417035-G-T
Variant summary
Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001035.3(RYR2):c.774-14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,612,906 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).
Frequency
Consequence
NM_001035.3 intron
Scores
Clinical Significance
Conservation
Publications
- arrhythmogenic right ventricular dysplasia 2Inheritance: AD Classification: DEFINITIVE, NO_KNOWN Submitted by: Laboratory for Molecular Medicine, Ambry Genetics
- catecholaminergic polymorphic ventricular tachycardiaInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P
- catecholaminergic polymorphic ventricular tachycardia 1Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- hypertrophic cardiomyopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen
- arrhythmogenic right ventricular cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.774-14G>T | intron_variant | Intron 10 of 104 | 1 | NM_001035.3 | ENSP00000355533.2 | |||
RYR2 | ENST00000661330.2 | c.774-14G>T | intron_variant | Intron 10 of 105 | ENSP00000499393.2 | |||||
RYR2 | ENST00000609119.2 | n.774-14G>T | intron_variant | Intron 10 of 103 | 5 | ENSP00000499659.2 |
Frequencies
GnomAD3 genomes AF: 0.000276 AC: 42AN: 152094Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000723 AC: 18AN: 248898 AF XY: 0.0000593 show subpopulations
GnomAD4 exome AF: 0.0000288 AC: 42AN: 1460692Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 726722 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000276 AC: 42AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74414 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not specified Uncertain:1
The c.774-14G>T variant in RYR2 has not been previously reported in individuals with cardiomyopathy but has been identified in 6/9594 African chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs37 0114411). This variant is located in the 3' splice region. Computational tools p redict some impact to splicing. However, this information is not predictive enou gh to determine pathogenicity. In summary, the clinical significance of the c.77 4-14G>T variant is uncertain. -
Catecholaminergic polymorphic ventricular tachycardia Benign:1
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Cardiomyopathy Benign:1
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Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at