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NM_001035.3(RYR2):c.13782+20A>G AND not specified

Germline classification:
Benign (1 submission)
Last evaluated:
Dec 9, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001193404.9

Allele description [Variation Report for NM_001035.3(RYR2):c.13782+20A>G]

NM_001035.3(RYR2):c.13782+20A>G

Gene:
RYR2:ryanodine receptor 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_001035.3(RYR2):c.13782+20A>G
HGVS:
  • NC_000001.11:g.237792343A>G
  • NG_008799.3:g.755160A>G
  • NM_001035.3:c.13782+20A>GMANE SELECT
  • LRG_402t1:c.13782+20A>G
  • LRG_402:g.755160A>G
  • NC_000001.10:g.237955643A>G
  • NG_008799.2:g.754942A>G
  • NM_001035.2:c.13782+20A>G
Links:
dbSNP: rs368059068
NCBI 1000 Genomes Browser:
rs368059068
Molecular consequence:
  • NM_001035.3:c.13782+20A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001362194Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Benign
(Dec 9, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362194.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: RYR2 c.13782+20A>G alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes a cryptic 5 donor site. Two predict the variant weakens a cryptic 5 donor site. Two predict the variant no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00034 in 223180 control chromosomes, predominantly at a frequency of 0.005 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 200 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 a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.13782+20A>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024