Variant: NM_000018.4(ACADVL):c.652_682dup (p.Ile228fs)

CA8337802

581080 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: eb7fde51-c627-4c18-93d8-c6bbfb1df4b0

Approved on: 2022-12-14

Published on: 2022-12-14

HGVS expressions

NM_000018.4:c.652_682dup
NM_000018.4(ACADVL):c.652_682dup (p.Ile228fs)
NC_000017.11:g.7221981_7222011dup
CM000679.2:g.7221981_7222011dup
NC_000017.10:g.7125300_7125330dup
CM000679.1:g.7125300_7125330dup
NC_000017.9:g.7066024_7066054dup
NG_007975.1:g.7148_7178dup
NG_008391.2:g.3040_3070dup
ENST00000356839.10:c.652_682dup
ENST00000322910.9:c.*607_*637dup
ENST00000350303.9:c.586_616dup
ENST00000356839.9:c.652_682dup
ENST00000543245.6:c.721_751dup
ENST00000577191.5:n.729_759dup
ENST00000577857.5:n.468_498dup
ENST00000579286.5:n.833_863dup
ENST00000580365.1:n.383_413dup
ENST00000581378.5:n.370_400dup
ENST00000582379.1:n.36_66dup
ENST00000583760.1:n.434_464dup
NM_000018.3:c.652_682dup
NM_001033859.2:c.586_616dup
NM_001270447.1:c.721_751dup
NM_001270448.1:c.424_454dup
NM_001033859.3:c.586_616dup
NM_001270447.2:c.721_751dup
NM_001270448.2:c.424_454dup

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.652_682dup (p.Ile228ArgfsTer35) variant in ACADVL is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 9/20 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). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+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: PM2_supporting, PVS1 (ACADVL VCEP specifications version 1; approved November 8, 2021).

Met criteria codes

• PM2_Supporting: This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
• PVS1: The c.652_682dup (p.Ile228ArgfsTer35) variant in ACADVL is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 9/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).