1-237610751-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001035.3(RYR2):c.4684-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,582,360 control chromosomes in the GnomAD database, including 1,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 710 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 681 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Splicing: ADA: 0.00002065

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.58

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-237610751-C-T is Benign according to our data. Variant chr1-237610751-C-T is described in ClinVar as [Benign]. Clinvar id is 43791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237610751-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3 link	c.4684-11C>T		intron_variant	Intron 35 of 104	ENST00000366574.7	NP_001026.2	Q92736-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RYR2	ENST00000366574.7 link	c.4684-11C>T	intron_variant	Intron 35 of 104	1	NM_001035.3	ENSP00000355533.2	Q92736-1
RYR2	ENST00000609119.2 link	n.4684-11C>T	intron_variant	Intron 35 of 103	5		ENSP00000499659.2	A0A590UK06
RYR2	ENST00000660292.2 link	c.4684-11C>T	intron_variant	Intron 35 of 105			ENSP00000499787.2	A0A590UKB7
RYR2	ENST00000659194.3 link	c.4684-11C>T	intron_variant	Intron 35 of 104			ENSP00000499653.3	A0A590UJZ8

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8093

AN:

151978

Hom.:

706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00888

Gnomad SAS

AF:

0.0202

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0159

AC:

3390

AN:

213648

Hom.:

258

AF XY:

0.0133

AC XY:

1521

AN XY:

114756

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.00779

Gnomad ASJ exome

AF:

0.000217

Gnomad EAS exome

AF:

0.00673

Gnomad SAS exome

AF:

0.0176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000644

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00682

AC:

9760

AN:

1430266

Hom.:

681

Cov.:

AF XY:

0.00649

AC XY:

4597

AN XY:

708220

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.00847

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.00338

Gnomad4 SAS exome

AF:

0.0177

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000380

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0533

AC:

8110

AN:

152094

Hom.:

710

Cov.:

AF XY:

0.0517

AC XY:

3847

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.0161

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00871

Gnomad4 SAS

AF:

0.0194

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0495

Hom.:

128

Bravo

AF:

0.0599

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 09, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cardiomyopathy

Benign:1

Mar 15, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arrhythmogenic right ventricular dysplasia 2

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.55

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over