NM_004453.3(ETFDH):c.1285+1G>A AND Glutaric aciduria, type 2

Clinical significance:Likely pathogenic (Last evaluated: Aug 16, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000634893.1

Allele description [Variation Report for NM_004453.3(ETFDH):c.1285+1G>A]

NM_004453.3(ETFDH):c.1285+1G>A

Gene:
ETFDH:electron transfer flavoprotein dehydrogenase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q32.1
Genomic location:
Preferred name:
NM_004453.3(ETFDH):c.1285+1G>A
HGVS:
  • NC_000004.12:g.158703592G>A
  • NG_007078.2:g.36251G>A
  • NM_004453.3:c.1285+1G>A
  • NC_000004.11:g.159624744G>A
Links:
dbSNP: rs767046886
NCBI 1000 Genomes Browser:
rs767046886
Molecular consequence:
  • NM_004453.3:c.1285+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Glutaric aciduria, type 2 (MADD)
Synonyms:
GA II; GLUTARIC ACIDURIA II; Multiple Acyl Coenzyme A Dehydrogenase Deficiency
Identifiers:
MedGen: C0268596; Orphanet: 26791; OMIM: 231680

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000756260Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 16, 2017)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency.

Kim SH, Scott SA, Bennett MJ, Carson RP, Fessel J, Brown HA, Ess KC.

PLoS Genet. 2013 Jun;9(6):e1003563. doi: 10.1371/journal.pgen.1003563. Epub 2013 Jun 13.

PubMed [citation]
PMID:
23785301
PMCID:
PMC3681725

Electron transfer flavoprotein deficiency: functional and molecular aspects.

Schiff M, Froissart R, Olsen RK, Acquaviva C, Vianey-Saban C.

Mol Genet Metab. 2006 Jun;88(2):153-8. Epub 2006 Feb 28.

PubMed [citation]
PMID:
16510302
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000756260.1

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

Description

This sequence change affects a donor splice site in intron 10 of the ETFDH gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs767046886, ExAC 0.002%). This variant has not been reported in the literature in individuals with ETFDH-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ETFDH are known to be pathogenic (PMID: 16510302, 23785301). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Mar 30, 2019

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