rs145140335

Positions:

• chr1-237643306-GT-G
• chr1-237643306-GT-GTT
• chr1-237643306-GT-GTTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001035.3(RYR2):​c.7222-12del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,580,562 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-237643306-GT-G is Benign according to our data. Variant chr1-237643306-GT-G is described in ClinVar as [Benign]. Clinvar id is 2187857.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-237643306-GT-G is described in Lovd as [Benign].
• BS2: High AC in GnomAdExome4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.7222-12del		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.7222-12del		intron_variant		1	NM_001035.3	P1
RYR2	ENST00000659194.3	c.7222-12del		intron_variant
RYR2	ENST00000660292.2	c.7222-12del		intron_variant
RYR2	ENST00000609119.2	c.7222-12del		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151454 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000329 AC: 47 AN: 1429108 Hom.: 0 Cov.: 30 AF XY: 0.0000310 AC XY: 22 AN XY: 710120

Gnomad4 AFR exome AF: 0.0000307

Gnomad4 AMR exome AF: 0.0000232

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000303

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151454 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73938

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145140335; hg19: chr1-237806606;