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NC_000017.11:g.7221954del AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jun 27, 2023
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:
RCV001239427.16

Allele description [Variation Report for NC_000017.11:g.7221954del]

NC_000017.11:g.7221954del

Gene:
ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NC_000017.11:g.7221954del
HGVS:
  • NC_000017.11:g.7221954del
  • NG_007975.1:g.7121del
  • NG_008391.2:g.3100del
  • NG_008391.3:g.3099del
  • NC_000017.10:g.7125270del
  • NC_000017.10:g.7125273del
  • NM_000018.3:c.625del
Links:
dbSNP: rs2071251239
NCBI 1000 Genomes Browser:
rs2071251239

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
SCV001412302Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 26, 2019) 		germlineclinical testing

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

SCV003936879ClinGen ACADVL Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(clingen acadvl acmg specifications v1)		Likely pathogenic
(Jun 27, 2023) 		germlinecuration

Citation Link

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Summary from all submissions

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

Citations

PubMed

Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

Andresen BS, Olpin S, Poorthuis BJ, Scholte HR, Vianey-Saban C, Wanders R, Ijlst L, Morris A, Pourfarzam M, Bartlett K, Baumgartner ER, deKlerk JB, Schroeder LD, Corydon TJ, Lund H, Winter V, Bross P, Bolund L, Gregersen N.

Am J Hum Genet. 1999 Feb;64(2):479-94.

PubMed [citation]
PMID:
9973285
PMCID:
PMC1377757

Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse.

Cox KB, Hamm DA, Millington DS, Matern D, Vockley J, Rinaldo P, Pinkert CA, Rhead WJ, Lindsey JR, Wood PA.

Hum Mol Genet. 2001 Sep 15;10(19):2069-77.

PubMed [citation]
PMID:
11590124
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001412302.5

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

Description

This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu209Argfs*8) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ACADVL-related conditions. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124).

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

From ClinGen ACADVL Variant Curation Expert Panel, ClinGen, SCV003936879.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000018.3(ACADVL):c.625del (p.Glu209ArgfsTer8) variant in ACADVL is a frameshift variant predicted cause a premature stop codon in biologically-relevant-exon 8/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Supporting.

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

Last Updated: Nov 3, 2024