Variant: NM_000018.4(ACADVL):c.644_647del (p.Phe214_Cys215insTer)

CA16041862

370717 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: fecc3e09-96c1-4257-830b-a6a0ef2718dc

Approved on: 2022-12-14

Published on: 2022-12-14

HGVS expressions

NM_000018.4:c.644_647delGTCT
NM_000018.4:c.644_647del
NM_000018.4(ACADVL):c.644_647del (p.Phe214_Cys215insTer)
NC_000017.11:g.7221973_7221976del
CM000679.2:g.7221973_7221976del
NC_000017.10:g.7125292_7125295del
CM000679.1:g.7125292_7125295del
NC_000017.9:g.7066016_7066019del
NG_007975.1:g.7140_7143del
NG_008391.2:g.3078_3081del
ENST00000356839.10:c.644_647del
ENST00000322910.9:c.*599_*602del
ENST00000350303.9:c.578_581del
ENST00000356839.9:c.644_647del
ENST00000543245.6:c.713_716del
ENST00000577191.5:n.721_724del
ENST00000577857.5:n.460_463del
ENST00000579286.5:n.825_828del
ENST00000580365.1:n.375_378del
ENST00000581378.5:n.362_365del
ENST00000581562.5:n.546_549del
ENST00000582379.1:n.28_31del
ENST00000583312.5:c.659_662del
ENST00000583760.1:n.426_429del
NM_000018.3:c.644_647del
NM_001033859.2:c.578_581del
NM_001270447.1:c.713_716del
NM_001270448.1:c.416_419del
NM_001033859.3:c.578_581del
NM_001270447.2:c.713_716del
NM_001270448.2:c.416_419del

Pathogenic

• Met criteria codes: PP4 PVS1 PM2_Supporting

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The c.644_647del (p.Phe214_Cys215insTer) variant in ACADVL is a frameshift variant predicted to 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). The highest population minor allele frequency in gnomAD v3.1.2 is 0.00006549 in Latino/Admixed American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). At least one patient with this variant displayed enzyme levels which is highly specific for VLCAD (PP4, PMID: 15210884). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the PVS1, PM2, PP4. (ACADVL VCEP specifications version 1; approved November 8, 2021).

Met criteria codes

• PP4: At least one patient with this variant displayed enzyme levels which is highly specific for VLCAD (PP4_supporting, PMID: 15210884).
• PVS1: The c.644_647del (p.Phe214_Cys215insTer) variant in ACADVL is a frameshift variant predicted to 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).
• PM2_Supporting: The highest population minor allele frequency in gnomAD v3.1.2 is 0.00006549 in Latino/Admixed American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).