Variant: NM_000018.4(ACADVL):c.128del (p.Gly43fs)

CA916083526

857574 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 9c6be044-a8fa-4238-8629-9d3c42852cc6

HGVS expressions

NM_000018.4:c.128del
NM_000018.4(ACADVL):c.128del (p.Gly43fs)
NC_000017.11:g.7220187del
CM000679.2:g.7220187del
NC_000017.10:g.7123506del
CM000679.1:g.7123506del
NC_000017.9:g.7064230del
NG_007975.1:g.5354del
NG_008391.2:g.4868del
ENST00000356839.10:c.128del
ENST00000322910.9:c.*83del
ENST00000350303.9:c.128del
ENST00000356839.9:c.128del
ENST00000543245.6:c.197del
ENST00000577191.5:n.205del
ENST00000577857.5:n.218del
ENST00000578269.5:n.235del
ENST00000578421.1:n.262del
ENST00000579286.5:n.235del
ENST00000579886.2:c.128del
ENST00000580263.5:n.218del
ENST00000581562.5:n.175del
ENST00000582056.5:n.218del
ENST00000582356.5:n.253del
ENST00000583312.5:c.128del
ENST00000584103.5:c.128del
NM_000018.3:c.128del
NM_001033859.2:c.128del
NM_001270447.1:c.197del
NM_001270448.1:c.-101del
NM_001033859.3:c.128del
NM_001270447.2:c.197del
NM_001270448.2:c.-101del

Likely Pathogenic

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

• Met criteria codes: PVS1 PM2_Supporting

• Not Met criteria codes: PS1 PM1 PM4 PM5 BP7

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.128del (p.Gly43Valfs*18) (NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 2/20 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 2.1.1 (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 VLCADD. In summary, this variant has been classified as likely pathogenic for autosomal recessive very long chain acyl-CoA dehydrogenase deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Curation Expert Panel: PVS1, PM2_Supporting (ACADVL VCEP specifications v2.0; Approved on 11/10/2021).

Met criteria codes

• PVS1: PVS1 met. The c.128del (p.Gly43Valfs*18) (NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 2/20 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 2.1.1 (PM2_Supporting).

Not Met criteria codes

• PS1: Criterion not met because variant is a deletion predicted to result in a frameshift and premature termination codon.
• PM1: PM1 not met. This variant does not reside within a region of ACADVL that is defined as a mutational hotspot or critical functional domain by the ClinGen ACADVL VCEP.
• PM4: Criterion not met because variant is a deletion predicted to result in a frameshift and premature termination codon.
• PM5: Criterion not met because variant is a deletion predicted to result in a frameshift and premature termination codon.
• BP7: Criterion not met because variant is a deletion predicted to result in a frameshift and premature termination codon.

Approved on: 2022-04-06

Published on: 2022-07-12