NM_015560.2(OPA1):c.1325A>C (p.Asp442Ala) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Oct 17, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000484153.1

Allele description [Variation Report for NM_015560.2(OPA1):c.1325A>C (p.Asp442Ala)]

NM_015560.2(OPA1):c.1325A>C (p.Asp442Ala)

Gene:
OPA1:OPA1 mitochondrial dynamin like GTPase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q29
Genomic location:
Preferred name:
NM_015560.2(OPA1):c.1325A>C (p.Asp442Ala)
HGVS:
  • NC_000003.12:g.193643987A>C
  • NG_011605.1:g.55844A>C
  • NM_001354663.2:c.956A>C
  • NM_001354664.2:c.953A>C
  • NM_015560.2:c.1325A>C
  • NM_130831.3:c.1217A>C
  • NM_130832.3:c.1271A>C
  • NM_130833.2:c.1328A>C
  • NM_130834.3:c.1379A>C
  • NM_130835.2:c.1382A>C
  • NM_130836.3:c.1436A>C
  • NM_130837.2:c.1490A>C
  • NP_001341592.1:p.Asp319Ala
  • NP_001341593.1:p.Asp318Ala
  • NP_056375.2:p.Asp442Ala
  • NP_570844.1:p.Asp406Ala
  • NP_570845.1:p.Asp424Ala
  • NP_570846.1:p.Asp443Ala
  • NP_570847.2:p.Asp460Ala
  • NP_570848.1:p.Asp461Ala
  • NP_570849.2:p.Asp479Ala
  • NP_570850.2:p.Asp497Ala
  • LRG_337t1:c.1325A>C
  • LRG_337t2:c.1490A>C
  • LRG_337:g.55844A>C
  • LRG_337p1:p.Asp442Ala
  • LRG_337p2:p.Asp497Ala
  • NC_000003.11:g.193361776A>C
Protein change:
D318A
Links:
dbSNP: rs1064795743
NCBI 1000 Genomes Browser:
rs1064795743
Molecular consequence:
  • NM_001354663.2:c.956A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354664.2:c.953A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015560.2:c.1325A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130831.3:c.1217A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130832.3:c.1271A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130833.2:c.1328A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130834.3:c.1379A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130835.2:c.1382A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130836.3:c.1436A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_130837.2:c.1490A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000571849GeneDxcriteria provided, single submitter
Likely pathogenic
(Oct 17, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000571849.3

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

Description

A novel D442A variant that is likely pathogenic was identified in the OPA1 gene. It has not been published as apathogenic variant, nor has it been reported as a benign variant to our knowledge. The D442A variant was notobserved in approximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The D442A variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differin polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved acrossspecies, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missensevariants in nearby residues (Q437R, G439V, R445H) have been reported in the Human Gene Mutation Database inassociation with OPA1-related disorders (Stenson et al., 2014), supporting the functional importance of this region ofthe protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Feb 27, 2021

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