NM_001035.3(RYR2):c.11880+13_11880+16del AND not specified

Germline classification:: Benign (4 submissions)
Last evaluated:: Aug 26, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000154647.16

Allele description [Variation Report for NM_001035.3(RYR2):c.11880+13_11880+16del]

NM_001035.3(RYR2):c.11880+13_11880+16del

Gene:

RYR2:ryanodine receptor 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_001035.3(RYR2):c.11880+13_11880+16del

HGVS:

NC_000001.11:g.237778783_237778786del
NG_008799.3:g.741600_741603del
NM_001035.3:c.11880+13_11880+16delMANE SELECT
LRG_402t1:c.11880+13_11880+16del
LRG_402:g.741600_741603del
NC_000001.10:g.237942083_237942086del
NC_000001.10:g.237942083_237942086delACTG
NG_008799.2:g.741382_741385del
NM_001035.2:c.11880+13_11880+16del
NM_001035.2:c.11880+13_11880+16delACTG

Links:

dbSNP: rs199562036

NCBI 1000 Genomes Browser:

rs199562036

Molecular consequence:

NM_001035.3:c.11880+13_11880+16del - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000204322	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (May 30, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000235019	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Dec 6, 2013)	germline	clinical testing	Citation Link,
SCV001360982	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Aug 26, 2019)	germline	clinical testing	Citation Link,
SCV001925692	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	37	37	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204322.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	37	not provided	not provided	clinical testing	PubMed (1)

Description

11880+13_11880+16delACTG in intron 88 of RYR2: This variant is not expected to h ave clinical significance because it is not located within the splice consensus sequence and has been identified in 1.6% (125/7922) of European American chromos omes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		37	not provided	37	not provided

From GeneDx, SCV000235019.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The variant is found in ARVC, CPVT, POSTMORTEM, ARRHYTHMIA, CARDIOMYOPATHY panel(s).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360982.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: RYR2 c.11880+13_11880+16delACTG alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. The variant allele was found at a frequency of 0.011 in 248142 control chromosomes in the gnomAD database, including 25 homozygotes. The observed variant frequency is approximately 443 fold of the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001925692.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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