rs2819742

Positions:

• chr1-237826822-A-G
• chr1-237826822-A-T

Variant summary

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

The NM_001035.3(RYR2):​c.14591-1559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,000 control chromosomes in the GnomAD database, including 39,615 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 0.70 (39615 hom., cov: 31)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.14591-1559A>G		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.14591-1559A>G		intron_variant		1	NM_001035.3	P1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106890 AN: 151882 Hom.: 39549 Cov.: 31

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.704 AC: 107021 AN: 152000 Hom.: 39615 Cov.: 31 AF XY: 0.704 AC XY: 52298 AN XY: 74292

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.719

Alfa AF: 0.616 Hom.: 67093

Bravo AF: 0.718

Asia WGS AF: 0.872 AC: 3032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.54

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: rs2819742; hg19: chr1-237990122;