Variant: NM_000018.2(ACADVL):c.343delG (p.Glu115Lysfs)

CA220206

1624 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: e1a7f305-d1e3-4e8b-9d38-0645f61fc98e

Approved on: 2021-11-09

Published on: 2022-04-06

HGVS expressions

NM_000018.2(ACADVL):c.343delG (p.Glu115Lysfs)
NC_000017.11:g.7220924del
CM000679.2:g.7220924del
NC_000017.10:g.7124243del
CM000679.1:g.7124243del
NC_000017.9:g.7064967del
NG_007975.1:g.6091del
NG_008391.2:g.4128del
ENST00000356839.10:c.343del
ENST00000322910.9:c.*298del
ENST00000350303.9:c.277del
ENST00000356839.9:c.343del
ENST00000543245.6:c.412del
ENST00000577191.5:n.420del
ENST00000577433.5:n.551del
ENST00000577857.5:n.293+94del
ENST00000579286.5:n.524del
ENST00000579886.2:c.202-21del
ENST00000580365.1:n.74del
ENST00000581378.5:n.42del
ENST00000581562.5:n.390del
ENST00000582056.5:n.526del
ENST00000582166.1:n.324del
ENST00000583312.5:c.343del
ENST00000584103.5:c.376del
NM_000018.3:c.343del
NM_001033859.2:c.277del
NM_001270447.1:c.412del
NM_001270448.1:c.115del
NM_000018.4:c.343del
NM_001033859.3:c.277del
NM_001270447.2:c.412del
NM_001270448.2:c.115del
NM_000018.4(ACADVL):c.343del

Pathogenic

• Met criteria codes: PP4 PVS1 PM2_Supporting

• Not Met criteria codes: PM3

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4(ACADVL): c.343del (p.Glu115Lysfs) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 6/20 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 v2.1.1 is 0.00004 in African population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). To our knowledge, functional assays have not been reported for this variant, however it has been reported in the literature in at least four individuals with VLCADD (PP4: PMID: 7479827, 31031081, 32778825). 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 ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_supporting, PP4.)

Met criteria codes

• PP4: Assertion of VLCAD deficiency (PMID: 31031081 & 7479827)
• PVS1: Frameshift exon 6/20
• PM2_Supporting: gnomAD frequency 0.001414%

Not Met criteria codes

• PM3: One copy (p.R613W) confirmed inherited from the mother. Deletion not confirmed from father. PM3_supporting NOT applied, because (p.R613W) variant is not curated by VCEP yet.