Variant: NM_000018.4(ACADVL):c.210dup (p.Lys71Ter)

CA312282

203588 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 3e8a4b38-5f5d-44b1-9603-c83cdceac5a3

HGVS expressions

NM_000018.4:c.210dup
NM_000018.4(ACADVL):c.210dup (p.Lys71Ter)
NC_000017.11:g.7220609dup
CM000679.2:g.7220609dup
NC_000017.10:g.7123928dup
CM000679.1:g.7123928dup
NC_000017.9:g.7064652dup
NG_007975.1:g.5776dup
NG_008391.2:g.4442dup
ENST00000356839.10:c.210dup
ENST00000322910.9:c.*165dup
ENST00000350303.9:c.144dup
ENST00000356839.9:c.210dup
ENST00000543245.6:c.279dup
ENST00000577191.5:n.287dup
ENST00000577433.5:n.418dup
ENST00000577857.5:n.229-157dup
ENST00000578269.5:n.657dup
ENST00000578421.1:n.418dup
ENST00000579286.5:n.391dup
ENST00000579886.2:c.201+83dup
ENST00000580263.5:n.374dup
ENST00000581562.5:n.257dup
ENST00000582056.5:n.300dup
ENST00000582166.1:n.98dup
ENST00000582356.5:n.409dup
ENST00000583312.5:c.210dup
ENST00000584103.5:c.210dup
NM_000018.3:c.210dup
NM_001033859.2:c.144dup
NM_001270447.1:c.279dup
NM_001270448.1:c.-19dup
NM_001033859.3:c.144dup
NM_001270447.2:c.279dup
NM_001270448.2:c.-19dup

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

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.210dup (p.Lys71Ter) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 4/20 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, (ACADVL VCEP specifications v2.0; Approved on 03/11/2021).

Met criteria codes

• PM2_Supporting: PM2_Supporting met. This variant is absent from gnomAD 2.1.1 (PM2_Supporting).
• PVS1: PVS1 met. The c.210dup (p.Lys71Ter) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 4/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).

Approved on: 2022-04-06

Published on: 2022-07-12