1-237712988-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.10323+1151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,166 control chromosomes in the GnomAD database, including 3,000 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 0.18 (3000 hom., cov: 32)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.10323+1151C>T		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.10323+1151C>T		intron_variant		1	NM_001035.3	P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26640 AN: 152048 Hom.: 2987 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.175 AC: 26679 AN: 152166 Hom.: 3000 Cov.: 32 AF XY: 0.182 AC XY: 13524 AN XY: 74386

Gnomad4 AFR AF: 0.0839

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.191

Alfa AF: 0.174 Hom.: 548

Bravo AF: 0.176

Asia WGS AF: 0.359 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.23
Dann	Benign	0.78

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: rs3766884; hg19: chr1-237876288;