Variant: NM_000018.4(ACADVL):c.190A>T (p.Lys64Ter)

CA397722281

1076425 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: dfd09649-6de8-4787-9cac-6162129f23e0

HGVS expressions

NM_000018.4:c.190A>T
NM_000018.4(ACADVL):c.190A>T (p.Lys64Ter)
NC_000017.11:g.7220515A>T
CM000679.2:g.7220515A>T
NC_000017.10:g.7123834A>T
CM000679.1:g.7123834A>T
NC_000017.9:g.7064558A>T
NG_007975.1:g.5682A>T
NG_008391.2:g.4536T>A
ENST00000356839.10:c.190A>T
ENST00000322910.9:c.*145A>T
ENST00000350303.9:c.139-89A>T
ENST00000356839.9:c.190A>T
ENST00000543245.6:c.259A>T
ENST00000577191.5:n.267A>T
ENST00000577433.5:n.324A>T
ENST00000577857.5:n.229-251A>T
ENST00000578269.5:n.563A>T
ENST00000578421.1:n.324A>T
ENST00000579286.5:n.297A>T
ENST00000579886.2:c.190A>T
ENST00000580263.5:n.280A>T
ENST00000581562.5:n.237A>T
ENST00000582056.5:n.280A>T
ENST00000582166.1:n.78A>T
ENST00000582356.5:n.315A>T
ENST00000583312.5:c.190A>T
ENST00000584103.5:c.190A>T
NM_000018.3:c.190A>T
NM_001033859.2:c.139-89A>T
NM_001270447.1:c.259A>T
NM_001270448.1:c.-39A>T
NM_001033859.3:c.139-89A>T
NM_001270447.2:c.259A>T
NM_001270448.2:c.-39A>T

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

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4(ACADVL):c.190A>T (p.Lys64Ter) variant in ACADVL is a nonsense predicted to cause a premature stop codon in biologically relevant exon 3/20 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, functional assays have not been reported for this variant. To our knowledge, this variant has not been reported in the literature in any individuals with VLCAD deficiency. 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, VCEP specifications v2.0; Approved 10-15-21.

Met criteria codes

• PVS1: The c.190A>T (p.Lys64Ter) ACADVL is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 3/20 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 (met). This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

Approved on: 2022-02-22

Published on: 2022-02-22