rs596502

Positions:

• chr1-237615609-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001035.3(RYR2):​c.5715+766C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,984 control chromosomes in the GnomAD database, including 38,041 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (38041 hom., cov: 31)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.5715+766C>T		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.5715+766C>T		intron_variant		1	NM_001035.3	P1
RYR2	ENST00000659194.3	c.5715+766C>T		intron_variant
RYR2	ENST00000660292.2	c.5715+766C>T		intron_variant
RYR2	ENST00000609119.2	c.5715+766C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102535 AN: 151866 Hom.: 38029 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.700

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.675 AC: 102569 AN: 151984 Hom.: 38041 Cov.: 31 AF XY: 0.678 AC XY: 50375 AN XY: 74308

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.699

Alfa AF: 0.783 Hom.: 45297

Bravo AF: 0.654

Asia WGS AF: 0.617 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs596502; hg19: chr1-237778909; COSMIC: COSV63673821;