Variant: NM_000018.4(ACADVL):c.1409del (p.Leu470fs)

CA1139665152

938242 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 4e57b5cd-cf40-49c5-b6f3-ed05ff653615

Approved on: 2022-09-13

Published on: 2022-09-13

HGVS expressions

NM_000018.4:c.1409del
NM_000018.4(ACADVL):c.1409del (p.Leu470fs)
NC_000017.11:g.7224044del
CM000679.2:g.7224044del
NC_000017.10:g.7127363del
CM000679.1:g.7127363del
NC_000017.9:g.7068087del
NG_007975.1:g.9211del
NG_008391.2:g.1007del
NG_033038.1:g.15501del
ENST00000356839.10:c.1409del
ENST00000322910.9:c.*1364del
ENST00000350303.9:c.1343del
ENST00000356839.9:c.1409del
ENST00000542255.6:n.267del
ENST00000543245.6:c.1478del
ENST00000578711.1:n.540del
ENST00000579425.5:n.525del
ENST00000579546.1:n.246del
ENST00000579894.5:n.120del
ENST00000583074.5:n.128del
ENST00000583850.5:n.184del
ENST00000583858.5:n.438del
ENST00000585203.6:n.600del
NM_000018.3:c.1409del
NM_001033859.2:c.1343del
NM_001270447.1:c.1478del
NM_001270448.1:c.1181del
NM_001033859.3:c.1343del
NM_001270447.2:c.1478del
NM_001270448.2:c.1181del

Likely Pathogenic

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

• Met criteria codes: PVS1 PM2_Supporting

Expert Panel

ACADVL VCEP

Criteria Specification Information

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

Evidence submitted by expert panel

ACADVL VCEP

The c.1409del (p.Leu470Argfs*22) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 14/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9328975, 11590124). To our knowledge, this variant has not been reported in the literature in any individuals with VLCADD. To our knowledge, functional assays have not been reported for this variant. PM2_Supporting is met. This variant is absent from gnomAD v2.1.1 (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, (ClinGen ACADVL VCEP specifications version#1.0; approved 08-08-22).

Met criteria codes

• PVS1: PVS1 is met. The c.1409del (p.Leu470Argfs*22) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 14/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124).
• PM2_Supporting: PM2_Supporting is met. This variant is absent from gnomAD v2.1.1 (PM2_Supporting).