rs773475551

Variant names:

• chr1-237650060-C-A
• NM_001035.3:c.7696C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-237650060-C-A
• chr1-237650060-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP6_Moderate BP7

The NM_001035.3(RYR2):​c.7696C>A​(p.Arg2566Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R2566R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RYR2 NM_001035.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.63

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-237650060-C-A is Benign according to our data. Variant chr1-237650060-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3073314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.63 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3	c.7696C>A	p.Arg2566Arg	synonymous_variant	Exon 50 of 105	ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.7696C>A	p.Arg2566Arg	synonymous_variant	Exon 50 of 105	1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.7696C>A		non_coding_transcript_exon_variant	Exon 50 of 104	5		ENSP00000499659.2
RYR2	ENST00000660292.2	c.7696C>A	p.Arg2566Arg	synonymous_variant	Exon 50 of 106			ENSP00000499787.2
RYR2	ENST00000659194.3	c.7696C>A	p.Arg2566Arg	synonymous_variant	Exon 50 of 105			ENSP00000499653.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia Benign:1

Sep 04, 2023

All of Us Research Program, National Institutes of Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	9.5
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-237813360;