Variant: NM_000018.4(ACADVL):c.1896dup (p.Asn633fs)

CA1139665163

932838 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 73838e8a-8ff2-45df-9ff6-868dad2283ee

Approved on: 2023-02-14

Published on: 2023-02-14

HGVS expressions

NM_000018.4:c.1896dup
NM_000018.4(ACADVL):c.1896dup (p.Asn633fs)
NC_000017.11:g.7225025dup
CM000679.2:g.7225025dup
NC_000017.10:g.7128344dup
CM000679.1:g.7128344dup
NC_000017.9:g.7069068dup
NG_007975.1:g.10192dup
NG_008391.2:g.26dup
NG_033038.1:g.14520dup
ENST00000356839.10:c.1896dup
ENST00000322910.9:c.*1851dup
ENST00000350303.9:c.1830dup
ENST00000356839.9:c.1896dup
ENST00000542255.6:n.775dup
ENST00000543245.6:c.1965dup
ENST00000578033.1:n.321dup
ENST00000578319.5:n.477dup
ENST00000578711.1:n.1521dup
ENST00000578809.5:n.468dup
ENST00000579425.5:n.1012dup
ENST00000583848.5:n.262dup
ENST00000583850.5:n.667dup
ENST00000583858.5:n.827dup
NM_000018.3:c.1896dup
NM_001033859.2:c.1830dup
NM_001270447.1:c.1965dup
NM_001270448.1:c.1668dup
NM_001033859.3:c.1830dup
NM_001270447.2:c.1965dup
NM_001270448.2:c.1668dup

Uncertain Significance

• Met criteria codes: PM2_Supporting PVS1_Moderate

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.1896dup (p.Asn633GlnfsTer57) variant in ACADVL is a frameshift variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and extend the protein by 32 amino acids (PVS1_Moderate). 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 VLCADD. In summary, this variant meets the criteria to be classified as UNCERTAIN SIGNIFICANCE 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_Moderate, PM2_Supporting (ClinGen ACADVL VCEP specifications version#1; 12-29-2022).

Met criteria codes

• PM2_Supporting: PM2_Supporting is met. This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
• PVS1_Moderate: PVS1_Moderate is met. The c.1896dup (p.Asn633GlnfsTer57) variant in ACADVL is a frameshift variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and extend the protein by 32 amino acids (PVS1_Strong).