Variant 1-237456575-ATTT-ATTTTT 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.1477-12_1477-11dupTT 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 0.011 ( 40 hom., cov: 0)

Exomes 𝑓: 0.0093 ( 2 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Not classified

Clinical Significance

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

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-A-ATT is Benign according to our data. Variant chr1-237456575-A-ATT is described in ClinVar as [Likely_benign]. Clinvar id is 1204240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3 link	c.1477-12_1477-11dupTT		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.1477-25_1477-24insTT	intron_variant	Intron 15 of 104	1	NM_001035.3	ENSP00000355533.2	Q92736-1
RYR2	ENST00000609119.2 link	n.1477-25_1477-24insTT	intron_variant	Intron 15 of 103	5		ENSP00000499659.2	A0A590UK06
RYR2	ENST00000660292.2 link	c.1477-25_1477-24insTT	intron_variant	Intron 15 of 105			ENSP00000499787.2	A0A590UKB7
RYR2	ENST00000659194.3 link	c.1477-25_1477-24insTT	intron_variant	Intron 15 of 104			ENSP00000499653.3	A0A590UJZ8

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1585

AN:

149082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.00521

Gnomad EAS

AF:

0.0997

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.000832

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.0113

GnomAD4 exome

AF:

0.00932

AC:

11267

AN:

1209390

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

5585

AN XY:

590404

show subpopulations

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.00991

Gnomad4 EAS exome

AF:

0.0690

Gnomad4 SAS exome

AF:

0.0221

Gnomad4 FIN exome

AF:

0.00602

Gnomad4 NFE exome

AF:

0.00617

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0106

AC:

1583

AN:

149164

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

841

AN XY:

72574

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.00607

Gnomad4 ASJ

AF:

0.00521

Gnomad4 EAS

AF:

0.0996

Gnomad4 SAS

AF:

0.0210

Gnomad4 FIN

AF:

0.000832

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.0107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 06, 2022

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 16, 2019

GeneDx

Significance: Likely 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

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