rs10925500

chr1-237729345-C-A

Variant summary

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

The NM_001035.3(RYR2):c.10839-915C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,092 control chromosomes in the GnomAD database, including 3,693 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 0.20 (3693 hom., cov: 32)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.10839-915C>A		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.10839-915C>A		intron_variant		1	NM_001035.3	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31135 AN: 151974 Hom.: 3692 Cov.: 32

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.205 AC: 31128 AN: 152092 Hom.: 3693 Cov.: 32 AF XY: 0.208 AC XY: 15442 AN XY: 74356

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.242

Alfa AF: 0.215 Hom.: 750

Bravo AF: 0.194

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.11
Dann	Benign	0.41

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: rs10925500; hg19: chr1-237892645;