rs2256242

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001035.3(RYR2):c.13476+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,592,510 control chromosomes in the GnomAD database, including 244,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28578 hom., cov: 32)

Exomes 𝑓: 0.54 ( 215985 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.231

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

arrhythmogenic right ventricular dysplasia 2
Inheritance: AD Classification: DEFINITIVE, NO_KNOWN Submitted by: Laboratory for Molecular Medicine, Ambry Genetics
catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P
catecholaminergic polymorphic ventricular tachycardia 1
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RYR2 links:

ENSG00000296715 (HGNC:):

ENSG00000296715 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-237788151-A-G is Benign according to our data. Variant chr1-237788151-A-G is described in ClinVar as [Benign]. Clinvar id is 93476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3 link	c.13476+16A>G		intron_variant	Intron 92 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.13476+16A>G	intron_variant	Intron 92 of 104	1	NM_001035.3	ENSP00000355533.2	Q92736-1
RYR2	ENST00000661330.2 link	c.13494+16A>G	intron_variant	Intron 93 of 105			ENSP00000499393.2	A0A590UJF6
RYR2	ENST00000609119.2 link	n.*4568+16A>G	intron_variant	Intron 91 of 103	5		ENSP00000499659.2	A0A590UK06

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91761

AN:

151962

Hom.:

28538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.763

Gnomad AMI

AF:

0.411

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.604

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.598

GnomAD2 exomes

AF:

0.558

AC:

132586

AN:

237710

AF XY:

0.558

show subpopulations

Gnomad AFR exome

AF:

0.772

Gnomad AMR exome

AF:

0.448

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.544

AC:

783735

AN:

1440430

Hom.:

215985

Cov.:

AF XY:

0.546

AC XY:

390835

AN XY:

716034

show subpopulations

African (AFR)

AF:

0.773

AC:

25423

AN:

32900

American (AMR)

AF:

0.461

AC:

19979

AN:

43292

Ashkenazi Jewish (ASJ)

AF:

0.624

AC:

16023

AN:

25678

East Asian (EAS)

AF:

0.684

AC:

26972

AN:

39420

South Asian (SAS)

AF:

0.599

AC:

50512

AN:

84262

European-Finnish (FIN)

AF:

0.511

AC:

27111

AN:

53064

Middle Eastern (MID)

AF:

0.641

AC:

3657

AN:

5706

European-Non Finnish (NFE)

AF:

0.529

AC:

580080

AN:

1096544

Other (OTH)

AF:

0.570

AC:

33978

AN:

59564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

16137

32273

48410

64546

80683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16640

33280

49920

66560

83200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.604

AC:

91856

AN:

152080

Hom.:

28578

Cov.:

AF XY:

0.601

AC XY:

44650

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.763

AC:

31650

AN:

41482

American (AMR)

AF:

0.510

AC:

7791

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

2093

AN:

3468

East Asian (EAS)

AF:

0.694

AC:

3581

AN:

5162

South Asian (SAS)

AF:

0.606

AC:

2920

AN:

4816

European-Finnish (FIN)

AF:

0.509

AC:

5389

AN:

10586

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.539

AC:

36617

AN:

67980

Other (OTH)

AF:

0.600

AC:

1265

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1824

3649

5473

7298

9122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.582

Hom.:

24451

Bravo

AF:

0.611

Asia WGS

AF:

0.622

AC:

2166

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

Oct 25, 2013

Eurofins Ntd Llc (ga)

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

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arrhythmogenic right ventricular dysplasia 2

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiac arrhythmia

Benign:1

Nov 07, 2021

Genome-Nilou Lab

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

-0.75

CADD

Benign

8.7

(source)

DANN

Benign

0.78

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over