1-237742270-CTTTTT-CTTTT

Variant summary

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

The NM_001035.3(RYR2):​c.11092-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,059,846 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 26)
Exomes 𝑓: 0.20 ( 1 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: -0.0580
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 1-237742270-CT-C is Benign according to our data. Variant chr1-237742270-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 43703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237742270-CT-C is described in Lovd as [Benign].
BA1
GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RYR2NM_001035.3 linkc.11092-11delT intron_variant Intron 79 of 104 ENST00000366574.7 NP_001026.2 Q92736-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RYR2ENST00000366574.7 linkc.11092-25delT intron_variant Intron 79 of 104 1 NM_001035.3 ENSP00000355533.2 Q92736-1
RYR2ENST00000661330.1 linkc.898-25delT intron_variant Intron 10 of 11 ENSP00000499393.2 A0A590UJF6
RYR2ENST00000609119.2 linkn.*2127-25delT intron_variant Intron 77 of 103 5 ENSP00000499659.2 A0A590UK06

Frequencies

GnomAD3 genomes
AF:
0.00335
AC:
463
AN:
138372
Hom.:
2
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.00209
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00331
Gnomad ASJ
AF:
0.00242
Gnomad EAS
AF:
0.00742
Gnomad SAS
AF:
0.00271
Gnomad FIN
AF:
0.0118
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00281
Gnomad OTH
AF:
0.00476
GnomAD4 exome
AF:
0.200
AC:
184655
AN:
921468
Hom.:
1
Cov.:
0
AF XY:
0.204
AC XY:
92704
AN XY:
455518
show subpopulations
Gnomad4 AFR exome
AF:
0.265
Gnomad4 AMR exome
AF:
0.243
Gnomad4 ASJ exome
AF:
0.261
Gnomad4 EAS exome
AF:
0.305
Gnomad4 SAS exome
AF:
0.210
Gnomad4 FIN exome
AF:
0.231
Gnomad4 NFE exome
AF:
0.189
Gnomad4 OTH exome
AF:
0.218
GnomAD4 genome
AF:
0.00339
AC:
469
AN:
138378
Hom.:
2
Cov.:
26
AF XY:
0.00401
AC XY:
269
AN XY:
67040
show subpopulations
Gnomad4 AFR
AF:
0.00219
Gnomad4 AMR
AF:
0.00331
Gnomad4 ASJ
AF:
0.00242
Gnomad4 EAS
AF:
0.00744
Gnomad4 SAS
AF:
0.00295
Gnomad4 FIN
AF:
0.0118
Gnomad4 NFE
AF:
0.00281
Gnomad4 OTH
AF:
0.00525

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
Oct 21, 2011
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

11092-11delT in intron 79 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. -

not provided Benign:1
Jul 15, 2020
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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.

Other links and lift over

dbSNP: rs397516499; hg19: chr1-237905570; API