Variant 1-237801833-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001035.3(RYR2):c.14091-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 0)

Exomes 𝑓: 0.099 ( 1 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.362

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:

RYR2 (HGNC:):

RYR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-237801833-AT-A is Benign according to our data. Variant chr1-237801833-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 43737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237801833-AT-A is described in Lovd as [Benign]. Variant chr1-237801833-AT-A is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3 linkuse as main transcript	c.14091-11delT		intron_variant		ENST00000366574.7	NP_001026.2	Q92736-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.14091-11delT		intron_variant		1	NM_001035.3	ENSP00000355533.2		Q92736-1
RYR2	ENST00000609119.2 linkuse as main transcript	n.*5183-11delT		intron_variant		5		ENSP00000499659.2		A0A590UK06

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

261

AN:

147836

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00122

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000786

Gnomad SAS

AF:

0.000634

Gnomad FIN

AF:

0.00568

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00347

GnomAD4 exome

AF:

0.0993

AC:

111640

AN:

1124718

Hom.:

Cov.:

AF XY:

0.0998

AC XY:

56002

AN XY:

561062

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.0904

Gnomad4 EAS exome

AF:

0.0545

Gnomad4 SAS exome

AF:

0.0974

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.0992

Gnomad4 OTH exome

AF:

0.0967

GnomAD4 genome

AF:

0.00179

AC:

265

AN:

147904

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

135

AN XY:

71976

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000789

Gnomad4 SAS

AF:

0.000635

Gnomad4 FIN

AF:

0.00568

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00393

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Sep 16, 2011

14091-11delT in intron 97 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. This variant has b een reported in dbSNP (rs72027983 & rs55683196) without frequency information. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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