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NM_130837.3(OPA1):c.556+1G>A AND Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 13, 2017
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:
RCV000853262.1

Allele description [Variation Report for NM_130837.3(OPA1):c.556+1G>A]

NM_130837.3(OPA1):c.556+1G>A

Gene:
OPA1:OPA1 mitochondrial dynamin like GTPase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q29
Genomic location:
Preferred name:
NM_130837.3(OPA1):c.556+1G>A
HGVS:
  • NC_000003.12:g.193617286G>A
  • NG_011605.1:g.29143G>A
  • NM_001354663.2:c.76+1516G>A
  • NM_001354664.2:c.184+1G>A
  • NM_015560.3:c.556+1G>A
  • NM_130831.3:c.448+1516G>A
  • NM_130832.3:c.449-498G>A
  • NM_130833.3:c.448+1516G>A
  • NM_130834.3:c.556+1G>A
  • NM_130835.3:c.449-498G>A
  • NM_130836.3:c.556+1G>A
  • NM_130837.3:c.556+1G>AMANE SELECT
  • LRG_337:g.29143G>A
  • NC_000003.11:g.193335075G>A
  • NM_130836.2:c.556+1G>A
Links:
dbSNP: rs1577162868
NCBI 1000 Genomes Browser:
rs1577162868
Molecular consequence:
  • NM_001354663.2:c.76+1516G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_130831.3:c.448+1516G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_130832.3:c.449-498G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_130833.3:c.448+1516G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_130835.3:c.449-498G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354664.2:c.184+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_015560.3:c.556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_130834.3:c.556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_130836.3:c.556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_130837.3:c.556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
1

Condition(s)

Name:
Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy
Identifiers:
MONDO: MONDO:0007429; MedGen: C3276549; OMIM: 125250

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000996089Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Dec 13, 2017) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV000996089.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

This canonical splice donor variant is predicted to alter the function of the protein. This variant is absent from population databases, thus it is presumed to be rare. The genomic position is highly conserved and in silico splicing algorithms predict the variant alters splicing mechanisms. Although this variant has not been previously reported in the literature to our knowledge, a similar pathogenic splice site variant located adjacent (c.556+2T>G) has been previously reported and splice site variants are well established as disease causing in the OPA1 gene (PMID: 26867657). Based on the combined evidence, the c.556+1G>A variant is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Jun 10, 2023