1-237527370-T-C

Variant names:

• chr1-237527370-T-C
• rs2779359
• NM_001035.3:c.2823-3057T>C

Variant summary

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

The NM_001035.3(RYR2):​c.2823-3057T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,738 control chromosomes in the GnomAD database, including 17,390 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 0.48 (17390 hom., cov: 33)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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 (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3	c.2823-3057T>C		intron_variant	Intron 24 of 104	ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.2823-3057T>C		intron_variant	Intron 24 of 104	1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.2823-3057T>C		intron_variant	Intron 24 of 103	5		ENSP00000499659.2
RYR2	ENST00000660292.2	c.2823-3057T>C		intron_variant	Intron 24 of 105			ENSP00000499787.2
RYR2	ENST00000659194.3	c.2823-3057T>C		intron_variant	Intron 24 of 104			ENSP00000499653.3

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72137 AN: 151618 Hom.: 17388 Cov.: 33

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.476 AC: 72163 AN: 151738 Hom.: 17390 Cov.: 33 AF XY: 0.477 AC XY: 35402 AN XY: 74160

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.451

Alfa AF: 0.486 Hom.: 2239

Bravo AF: 0.471

Asia WGS AF: 0.477 AC: 1657 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	4.4
DANN	Benign	0.76

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: rs2779359; hg19: chr1-237690670;