1-237283419-T-G

Position:

• chr1-237283419-T-G

Variant summary

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

The NM_001035.3(RYR2):​c.168+12803T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,944 control chromosomes in the GnomAD database, including 19,123 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 0.47 (19123 hom., cov: 32)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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]

RYR2 (HGNC:):

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 = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3	c.168+12803T>G		intron_variant		ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.168+12803T>G		intron_variant		1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.168+12803T>G		intron_variant		5		ENSP00000499659.2
RYR2	ENST00000660292.2	c.168+12803T>G		intron_variant				ENSP00000499787.2
RYR2	ENST00000659194.3	c.168+12803T>G		intron_variant				ENSP00000499653.3

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71994 AN: 151826 Hom.: 19085 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.474 AC: 72086 AN: 151944 Hom.: 19123 Cov.: 32 AF XY: 0.479 AC XY: 35578 AN XY: 74268

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.446

Alfa AF: 0.418 Hom.: 3237

Bravo AF: 0.479

Asia WGS AF: 0.652 AC: 2263 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	3.5
DANN	Benign	0.66

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: rs7526245; hg19: chr1-237446719; COSMIC: COSV63672884;