Variant: NM_000018.4(ACADVL):c.1389dup (p.Thr464fs)

CA220196

92275 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: f0d43ea4-04ab-47a0-9d03-524bdbf2fab0

HGVS expressions

NM_000018.4:c.1389dup
NM_000018.4(ACADVL):c.1389dup (p.Thr464fs)
NC_000017.11:g.7224024dup
CM000679.2:g.7224024dup
NC_000017.10:g.7127343dup
CM000679.1:g.7127343dup
NC_000017.9:g.7068067dup
NG_007975.1:g.9191dup
NG_008391.2:g.1030dup
NG_033038.1:g.15524dup
ENST00000356839.10:c.1389dup
ENST00000322910.9:c.*1344dup
ENST00000350303.9:c.1323dup
ENST00000356839.9:c.1389dup
ENST00000542255.6:n.247dup
ENST00000543245.6:c.1458dup
ENST00000578711.1:n.520dup
ENST00000579425.5:n.505dup
ENST00000579546.1:n.226dup
ENST00000579894.5:n.100dup
ENST00000583074.5:n.108dup
ENST00000583850.5:n.164dup
ENST00000583858.5:n.418dup
ENST00000585203.6:n.580dup
NM_000018.3:c.1389dup
NM_001033859.2:c.1323dup
NM_001270447.1:c.1458dup
NM_001270448.1:c.1161dup
NM_001033859.3:c.1323dup
NM_001270447.2:c.1458dup
NM_001270448.2:c.1161dup

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "[unknown]"

• 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.1389dup (p.Thr464AspfsTer3) 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). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). 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. 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; 08-04-2022).

Met criteria codes

• PVS1: PVS1 is met. The c.1389dup (p.Thr464AspfsTer3) variant in ACADVL is a nonsense 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).

Approved on: 2022-08-23

Published on: 2022-08-23