1-237456575-ATTT-ATTTTTTT
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_001035.3(RYR2):c.1477-14_1477-11dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000066 ( 0 hom. )
Consequence
RYR2
NM_001035.3 intron
NM_001035.3 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.43
Genes affected
RYR2 (HGNC:10484): (ryanodine receptor 2) This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
Variant 1-237456575-A-ATTTT is Benign according to our data. Variant chr1-237456575-A-ATTTT is described in ClinVar as [Likely_benign]. Clinvar id is 918143.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RYR2 | ENST00000366574.7 | c.1477-25_1477-24insTTTT | intron_variant | 1 | NM_001035.3 | ENSP00000355533.2 | ||||
| RYR2 | ENST00000609119.2 | n.1477-25_1477-24insTTTT | intron_variant | 5 | ENSP00000499659.2 | |||||
| RYR2 | ENST00000660292.2 | c.1477-25_1477-24insTTTT | intron_variant | ENSP00000499787.2 | ||||||
| RYR2 | ENST00000659194.3 | c.1477-25_1477-24insTTTT | intron_variant | ENSP00000499653.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
0
GnomAD4 exome AF: 0.00000657 AC: 8AN: 1216926Hom.: 0 Cov.: 0 AF XY: 0.0000118 AC XY: 7AN XY: 593934
GnomAD4 exome
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8
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1216926
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0
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7
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593934
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GnomAD4 genome
GnomAD4 genome
Cov.:
0
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 30, 2020 | Variant summary: RYR2 c.1477-14_1477-11dupTTTT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 142038 control chromosomes, however there are several other duplicaton and deletions of the polyT tract present in gnomad at a high frequency, suggesting the benign nature of the variant. To our knowledge, no occurrence of c.1477-14_1477-11dupTTTT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. - |
Computational scores
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Name
Calibrated prediction
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Prediction
BranchPoint Hunter
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at