Variant: NM_000018.4(ACADVL):c.343-1G>A

CA312290

203594 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 8fd36674-a2a5-46fb-a0e2-3cc54dea1366

Approved on: 2021-11-09

Published on: 2022-04-06

HGVS expressions

NM_000018.4:c.343-1G>A
NM_000018.4(ACADVL):c.343-1G>A
NC_000017.11:g.7220923G>A
CM000679.2:g.7220923G>A
NC_000017.10:g.7124242G>A
CM000679.1:g.7124242G>A
NC_000017.9:g.7064966G>A
NG_007975.1:g.6090G>A
NG_008391.2:g.4128C>T
ENST00000356839.10:c.343-1G>A
ENST00000322910.9:c.*298-1G>A
ENST00000350303.9:c.277-1G>A
ENST00000356839.9:c.343-1G>A
ENST00000543245.6:c.412-1G>A
ENST00000577191.5:n.420-1G>A
ENST00000577433.5:n.551-1G>A
ENST00000577857.5:n.293+93G>A
ENST00000579286.5:n.524-1G>A
ENST00000579886.2:c.202-22G>A
ENST00000580365.1:n.74-1G>A
ENST00000581378.5:n.42-1G>A
ENST00000581562.5:n.390-1G>A
ENST00000582056.5:n.525G>A
ENST00000582166.1:n.323G>A
ENST00000583312.5:c.343-1G>A
ENST00000584103.5:c.375G>A
NM_000018.3:c.343-1G>A
NM_001033859.2:c.277-1G>A
NM_001270447.1:c.412-1G>A
NM_001270448.1:c.115-1G>A
NM_001033859.3:c.277-1G>A
NM_001270447.2:c.412-1G>A
NM_001270448.2:c.115-1G>A

Pathogenic

• Met criteria codes: PP4_Moderate PVS1 PM2_Supporting

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The c.343-1G>A variant in ACADVL occurs within the canonical splice acceptor site of intron 5. It is predicted to cause skipping of biologically-relevant-exon 5/6, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant is reported in at least one patient with abnormal C14:1 (0.4-6.5 uM, 1-365 days), who also carried the pathogenic (p.V283A) variant (PP4_moderate: PMID: 31983732). 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_moderate).

Met criteria codes

• PP4_Moderate: PMID: 31983732; single case study C14:1 = 6.53, 0.36, 4.57 (1st day of life, 4th, 356th) compound heterozygote (with p.V283A; phase not determined) VLCAD enzyme activity not provided
• PVS1: Splice acceptor of intron 5
• PM2_Supporting: absent from population