NM_000182.5(HADHA):c.1967del (p.Ile655_Leu656insTer) AND Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: May 22, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000169001.2

Allele description [Variation Report for NM_000182.5(HADHA):c.1967del (p.Ile655_Leu656insTer)]

NM_000182.5(HADHA):c.1967del (p.Ile655_Leu656insTer)

Genes:
GAREM2:GRB2 associated regulator of MAPK1 subtype 2 [Gene - OMIM - HGNC]
HADHA:hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p23.3
Genomic location:
Preferred name:
NM_000182.5(HADHA):c.1967del (p.Ile655_Leu656insTer)
HGVS:
  • NC_000002.12:g.26192346del
  • NG_007121.1:g.57278del
  • NM_000182.5:c.1967delMANE SELECT
  • NP_000173.2:p.Ile655_Leu656insTer
  • LRG_747t1:c.1967del
  • LRG_747p1:p.Ile655_Leu656insTer
  • NC_000002.11:g.26415215del
  • NM_000182.4:c.1967del
  • NM_000182.4:c.1967delT
Links:
dbSNP: rs779113356
NCBI 1000 Genomes Browser:
rs779113356
Molecular consequence:
  • NM_000182.5:c.1967del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Synonyms:
Deficiency of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase
Identifiers:
MONDO: MONDO:0012173; MedGen: C3711645; Orphanet: 5; OMIM: 609016

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000220140Counsylcriteria provided, single submitter
Likely pathogenic
(Mar 4, 2014)
unknownliterature only

PubMed (2)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV000695944Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(May 22, 2017)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.

Ibdah JA, Bennett MJ, Rinaldo P, Zhao Y, Gibson B, Sims HF, Strauss AW.

N Engl J Med. 1999 Jun 3;340(22):1723-31.

PubMed [citation]
PMID:
10352164

Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiency.

Boutron A, Acquaviva C, Vianey-Saban C, de Lonlay P, de Baulny HO, Guffon N, Dobbelaere D, Feillet F, Labarthe F, Lamireau D, Cano A, de Villemeur TB, Munnich A, Saudubray JM, Rabier D, Rigal O, Brivet M.

Mol Genet Metab. 2011 Aug;103(4):341-8. doi: 10.1016/j.ymgme.2011.04.006. Epub 2011 Apr 19.

PubMed [citation]
PMID:
21549624

Details of each submission

From Counsyl, SCV000220140.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695944.1

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

Description

Variant summary: The HADHA c.1967delT (p.Leu656X) variant results in a premature termination codon, predicted to cause a truncated or absent HADHA protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/121390 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic HADHA variant (0.0019365). This variant has been reported in multiple patients as compound heterozygotes (Ibdah_!999 and Boutron_2011). One of patients showed 26% of residual LCHAD activity relative to the controls mean in fibroblasts and 2% of residual LKAT activity relative to the controls mean (Boutron_2011). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Oct 8, 2021

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