Variant: NM_000018.4(ACADVL):c.1532+1G>A

CA273297

166646 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 276a0259-f229-43a5-8219-d7d7ba720039

Approved on: 2022-12-14

Published on: 2022-12-14

HGVS expressions

NM_000018.4:c.1532+1G>A
NM_000018.4(ACADVL):c.1532+1G>A
NC_000017.11:g.7224244G>A
CM000679.2:g.7224244G>A
NC_000017.10:g.7127563G>A
CM000679.1:g.7127563G>A
NC_000017.9:g.7068287G>A
NG_007975.1:g.9411G>A
NG_008391.2:g.807C>T
NG_033038.1:g.15301C>T
ENST00000356839.10:c.1532+1G>A
ENST00000322910.9:c.*1487+1G>A
ENST00000350303.9:c.1466+1G>A
ENST00000356839.9:c.1532+1G>A
ENST00000542255.6:n.390+1G>A
ENST00000543245.6:c.1601+1G>A
ENST00000578319.5:n.27+1G>A
ENST00000578711.1:n.740G>A
ENST00000578809.5:n.28G>A
ENST00000579391.1:n.140+1G>A
ENST00000579425.5:n.648+1G>A
ENST00000579546.1:n.272-77G>A
ENST00000579894.5:n.319+1G>A
ENST00000583074.5:n.154-77G>A
ENST00000583850.5:n.307+1G>A
ENST00000583858.5:n.464-77G>A
ENST00000585203.6:n.723+1G>A
NM_000018.3:c.1532+1G>A
NM_001033859.2:c.1466+1G>A
NM_001270447.1:c.1601+1G>A
NM_001270448.1:c.1304+1G>A
NM_001033859.3:c.1466+1G>A
NM_001270447.2:c.1601+1G>A
NM_001270448.2:c.1304+1G>A

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

• Met criteria codes: PM2_Supporting PVS1

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The c.1532+1G>A variant in ACADVL occurs within the canonical splice donor/acceptor site (+/- 1,2) of intron 15. It is predicted to cause skipping of biologically-relevant-exon 15/20, resulting in a frameshift 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 is 0.000008801 in the European non-Finnish population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (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. (ACADVL VCEP specifications version 1; approved November 8, 2021)

Met criteria codes

• PM2_Supporting: The highest population minor allele frequency in gnomAD v2.1 is 0.000008801 in the European non-Finnish population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).
• PVS1: The c.1532+1G>A variant in ACADVL occurs within the canonical splice donor/acceptor site (+/- 1,2) of intron 15. It is predicted to cause skipping of biologically-relevant-exon 15/20, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).