1-237742270-CTTTTT-CTTTT

Variant names:

• chr1-237742270-CT-C
• rs397516499
• NM_001035.3:c.11092-11delT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001035.3(RYR2):​c.11092-11delT 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 1,059,846 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 26)
  • Exomes 𝑓: 0.20 (1 hom.)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0580

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 -16 ACMG points.

• BP6: Variant 1-237742270-CT-C is Benign according to our data. Variant chr1-237742270-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 43703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237742270-CT-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3	c.11092-11delT		intron_variant	Intron 79 of 104	ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.11092-25delT		intron_variant	Intron 79 of 104	1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000661330.1	c.898-25delT		intron_variant	Intron 10 of 11			ENSP00000499393.2
RYR2	ENST00000609119.2	n.*2127-25delT		intron_variant	Intron 77 of 103	5		ENSP00000499659.2

Frequencies

GnomAD3 genomes AF: 0.00335 AC: 463 AN: 138372 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.00209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00331

Gnomad ASJ AF: 0.00242

Gnomad EAS AF: 0.00742

Gnomad SAS AF: 0.00271

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.00476

GnomAD4 exome AF: 0.200 AC: 184655 AN: 921468 Hom.: 1 Cov.: 0 AF XY: 0.204 AC XY: 92704 AN XY: 455518

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.00339 AC: 469 AN: 138378 Hom.: 2 Cov.: 26 AF XY: 0.00401 AC XY: 269 AN XY: 67040

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00331

Gnomad4 ASJ AF: 0.00242

Gnomad4 EAS AF: 0.00744

Gnomad4 SAS AF: 0.00295

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.00281

Gnomad4 OTH AF: 0.00525

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Oct 21, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

11092-11delT in intron 79 of RYR2: This variant is not expected to have clinical significance because it is located outside the conserved +/- 1, 2 region of the splicing consensus sequence and as part of a polyT stretch. -

not provided Benign:1

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs397516499; hg19: chr1-237905570;