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NM_000018.4(ACADVL):c.1077+2T>A AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 22, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV002286687.2

Allele description [Variation Report for NM_000018.4(ACADVL):c.1077+2T>A]

NM_000018.4(ACADVL):c.1077+2T>A

Gene:
ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000018.4(ACADVL):c.1077+2T>A
HGVS:
  • NC_000017.11:g.7222867T>A
  • NG_007975.1:g.8034T>A
  • NG_008391.2:g.2184A>T
  • NG_008391.3:g.2183A>T
  • NM_000018.4:c.1077+2T>AMANE SELECT
  • NM_001033859.3:c.1011+2T>A
  • NM_001270447.2:c.1146+2T>A
  • NM_001270448.2:c.849+2T>A
  • NC_000017.10:g.7126186T>A
Molecular consequence:
  • NM_000018.4:c.1077+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001033859.3:c.1011+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001270447.2:c.1146+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001270448.2:c.849+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Very long chain acyl-CoA dehydrogenase deficiency (ACADVLD)
Synonyms:
VLCAD deficiency
Identifiers:
MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002576768ClinGen ACADVL Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(clingen acadvl acmg specifications v1)		Pathogenic
(Sep 22, 2022) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen ACADVL Variant Curation Expert Panel, ClinGen, SCV002576768.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.1077+2T>A (NM_000018.4) variant in ACADVL occurs within the canonical splice donor site (+/- 1,2) of intron 10. It is predicted to cause skipping of biologically-relevant-exon 10/20, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). This variant been reported in one individual with very long chain acyl-CoA dehydrogenase deficiency in the literature with decreased VLCAD enzyme activity (PP4_moderate; PMID: 30194637). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The ACADVL Variant Curation Expert Panel VCEP classified the variant as pathogenic based on PVS1, PM2_supporting, PP4_Moderate.

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

Last Updated: Jun 10, 2023