Variant 1-237456575-ATTT-ATT 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.1477-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.26 ( 5042 hom., cov: 0)

Exomes 𝑓: 0.23 ( 3292 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.43

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 -16 ACMG points.

BP6

Variant 1-237456575-AT-A is Benign according to our data. Variant chr1-237456575-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 43749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237456575-AT-A is described in Lovd as [Benign]. Variant chr1-237456575-AT-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3 link	c.1477-11delT		intron_variant	Intron 15 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.1477-24delT	intron_variant	Intron 15 of 104	1	NM_001035.3	ENSP00000355533.2	Q92736-1
RYR2	ENST00000609119.2 link	n.1477-24delT	intron_variant	Intron 15 of 103	5		ENSP00000499659.2	A0A590UK06
RYR2	ENST00000660292.2 link	c.1477-24delT	intron_variant	Intron 15 of 105			ENSP00000499787.2	A0A590UKB7
RYR2	ENST00000659194.3 link	c.1477-24delT	intron_variant	Intron 15 of 104			ENSP00000499653.3	A0A590UJZ8

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

38531

AN:

148980

Hom.:

5038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.247

GnomAD4 exome

AF:

0.226

AC:

268933

AN:

1188048

Hom.:

3292

Cov.:

AF XY:

0.227

AC XY:

131607

AN XY:

580136

show subpopulations

Gnomad4 AFR exome

AF:

0.289

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.259

AC:

38574

AN:

149064

Hom.:

5042

Cov.:

AF XY:

0.259

AC XY:

18809

AN XY:

72526

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.250

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Sep 16, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1477-11delT in intron 15 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 be en reported in dbSNP (rs60132900 & rs5781961) without frequency information. -

Sep 20, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:1

Nov 07, 2021

Genome-Nilou Lab

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

BranchPoint Hunter

3.0

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