NM_002495.3(NDUFS4):c.99-1G>A AND Leigh syndrome

Clinical significance:Pathogenic (Last evaluated: Feb 12, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000588112.1

Allele description [Variation Report for NM_002495.3(NDUFS4):c.99-1G>A]

NM_002495.3(NDUFS4):c.99-1G>A

Gene:
NDUFS4:NADH:ubiquinone oxidoreductase subunit S4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q11.2
Genomic location:
Preferred name:
NM_002495.3(NDUFS4):c.99-1G>A
HGVS:
  • NC_000005.10:g.53603451G>A
  • NG_008200.1:g.47817G>A
  • NM_002495.3:c.99-1G>A
  • NC_000005.9:g.52899281G>A
  • NM_002495.2:c.99-1G>A
Nucleotide change:
IVS1AS, G-A, -1
Links:
OMIM: 602694.0005; dbSNP: rs376281345
NCBI 1000 Genomes Browser:
rs376281345
Molecular consequence:
  • NM_002495.3:c.99-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Leigh syndrome (LS)
Synonyms:
Leigh Disease; Leigh's disease; Leigh's syndrome
Identifiers:
MedGen: C0023264; Orphanet: 506; OMIM: 256000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697980Integrated Genetics/Laboratory Corporation of Americacriteria provided, single submitter
Pathogenic
(Feb 12, 2016)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

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

Citations

PubMed

High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency.

Calvo SE, Tucker EJ, Compton AG, Kirby DM, Crawford G, Burtt NP, Rivas M, Guiducci C, Bruno DL, Goldberger OA, Redman MC, Wiltshire E, Wilson CJ, Altshuler D, Gabriel SB, Daly MJ, Thorburn DR, Mootha VK.

Nat Genet. 2010 Oct;42(10):851-8. doi: 10.1038/ng.659. Epub 2010 Sep 5.

PubMed [citation]
PMID:
20818383
PMCID:
PMC2977978

Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome.

Bénit P, Steffann J, Lebon S, Chretien D, Kadhom N, de Lonlay P, Goldenberg A, Dumez Y, Dommergues M, Rustin P, Munnich A, Rötig A.

Hum Genet. 2003 May;112(5-6):563-6. Epub 2003 Mar 4.

PubMed [citation]
PMID:
12616398
See all PubMed Citations (3)

Details of each submission

From Integrated Genetics/Laboratory Corporation of America, SCV000697980.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: The c.99-1G>A variant affects a conserved splice site nucleotide. One in-silico tool predicts damaging outcome for this variant. 5/5 programs in Alamut predict that this variant affects normal splicing, which is confirmed by RT-PCR in patients carrying this variant, showing the variant causes the complete skipping of exon 2. This variant is found in 2/120974 control chromosomes at a frequency of 0.0000165, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.00125). In addition, reputable database classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.

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

Last Updated: Mar 30, 2019

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