Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000018.4(ACADVL):c.887_888del (p.Pro296fs)

CA274249

189008 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 8783a60d-89ab-4b4e-a102-bd718c8e2f56

HGVS expressions

NM_000018.4:c.887_888del

NM_000018.4(ACADVL):c.887_888del (p.Pro296fs)

NC_000017.11:g.7222675_7222676del

CM000679.2:g.7222675_7222676del

NC_000017.10:g.7125994_7125995del

CM000679.1:g.7125994_7125995del

NC_000017.9:g.7066718_7066719del

NG_007975.1:g.7842_7843del

NG_008391.2:g.2375_2376del

ENST00000356839.10:c.887_888del

ENST00000322910.9:c.*842_*843del

ENST00000350303.9:c.821_822del

ENST00000356839.9:c.887_888del

ENST00000543245.6:c.956_957del

ENST00000578824.5:n.36_37del

ENST00000581378.5:n.605_606del

ENST00000582379.1:n.271_272del

NM_000018.3:c.887_888del

NM_001033859.2:c.821_822del

NM_001270447.1:c.956_957del

NM_001270448.1:c.659_660del

NM_001033859.3:c.821_822del

NM_001270447.2:c.956_957del

NM_001270448.2:c.659_660del

Likely Pathogenic

PVS1 PM2_Supporting

PP4

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specification: ClinGen ACADVL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.887_888del (p.Pro296ArgfsTer17) variant in ACADVL results in a frameshift predicted to cause a premature stop codon in biologically relevant exon 10/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). The highest population minor allele frequency in gnomAD is 0.00003 in the Latino population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) meeting this criterion (PM2_Supporting). This variant has also been reported in patients with phenotypes suggestive of a fatty acid oxidation defect (PMIDs: 10077518, 32778825). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on (PVS1+PM2_supporting).

PVS1

Frameshift exon 10/20

PM2_Supporting

The highest population MAF in gnomAD is 0.00003 in Latino population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001).

PP4

VLCADD not asserted

Approved on: 2023-06-13

Published on: 2023-06-13

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