Variant chr1-237759753-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001035.3(RYR2):c.11326-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,483,426 control chromosomes in the GnomAD database, including 363,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40736 hom., cov: 31)

Exomes 𝑓: 0.70 ( 322854 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0510

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-237759753-C-T is Benign according to our data. Variant chr1-237759753-C-T is described in ClinVar as [Benign]. Clinvar id is 257198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3 linkuse as main transcript	c.11326-23C>T		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.11326-23C>T	intron_variant	1	NM_001035.3	P1	Q92736-1
RYR2	ENST00000659194.3 linkuse as main transcript	c.11314-23C>T	intron_variant
RYR2	ENST00000660292.2 linkuse as main transcript	c.11314-23C>T	intron_variant
RYR2	ENST00000609119.2 linkuse as main transcript	c.*2418-23C>T	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

110940

AN:

151880

Hom.:

40687

Cov.:

show subpopulations

Gnomad AFR

AF:

0.794

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.723

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.755

GnomAD3 exomes

AF:

0.713

AC:

177132

AN:

248294

Hom.:

63411

AF XY:

0.709

AC XY:

95504

AN XY:

134714

show subpopulations

Gnomad AFR exome

AF:

0.800

Gnomad AMR exome

AF:

0.738

Gnomad ASJ exome

AF:

0.713

Gnomad EAS exome

AF:

0.779

Gnomad SAS exome

AF:

0.697

Gnomad FIN exome

AF:

0.740

Gnomad NFE exome

AF:

0.683

Gnomad OTH exome

AF:

0.713

GnomAD4 exome

AF:

0.695

AC:

925643

AN:

1331426

Hom.:

322854

Cov.:

AF XY:

0.695

AC XY:

465194

AN XY:

669826

show subpopulations

Gnomad4 AFR exome

AF:

0.796

Gnomad4 AMR exome

AF:

0.740

Gnomad4 ASJ exome

AF:

0.716

Gnomad4 EAS exome

AF:

0.793

Gnomad4 SAS exome

AF:

0.703

Gnomad4 FIN exome

AF:

0.735

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.713

GnomAD4 genome

AF:

0.731

AC:

111041

AN:

152000

Hom.:

40736

Cov.:

AF XY:

0.736

AC XY:

54680

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.794

Gnomad4 AMR

AF:

0.744

Gnomad4 ASJ

AF:

0.723

Gnomad4 EAS

AF:

0.789

Gnomad4 SAS

AF:

0.700

Gnomad4 FIN

AF:

0.753

Gnomad4 NFE

AF:

0.683

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.703

Hom.:

7677

Bravo

AF:

0.730

Asia WGS

AF:

0.769

AC:

2677

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Arrhythmogenic right ventricular dysplasia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Cardiac arrhythmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.5

DANN

Benign

0.79

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

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