Variant: NM_000018.4(ACADVL):c.1251del (p.Ser418fs)

CA2499224903

1073505 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: ed709b5f-bc3d-4070-a616-dfde5be00520

Approved on: 2022-12-14

Published on: 2022-12-14

HGVS expressions

NM_000018.4:c.1251del
NM_000018.4(ACADVL):c.1251del (p.Ser418fs)
NC_000017.11:g.7223712del
CM000679.2:g.7223712del
NC_000017.10:g.7127031del
CM000679.1:g.7127031del
NC_000017.9:g.7067755del
NG_007975.1:g.8879del
NG_008391.2:g.1339del
NG_033038.1:g.15833del
ENST00000356839.10:c.1251del
ENST00000322910.9:c.*1206del
ENST00000350303.9:c.1185del
ENST00000356839.9:c.1251del
ENST00000542255.6:n.109del
ENST00000543245.6:c.1320del
ENST00000578579.2:n.422del
ENST00000578711.1:n.208del
ENST00000578824.5:n.667del
ENST00000579425.5:n.275del
ENST00000579546.1:n.88del
ENST00000583850.5:n.26del
ENST00000583858.5:n.280del
ENST00000585203.6:n.459del
NM_000018.3:c.1251del
NM_001033859.2:c.1185del
NM_001270447.1:c.1320del
NM_001270448.1:c.1023del
NM_001033859.3:c.1185del
NM_001270447.2:c.1320del
NM_001270448.2:c.1023del

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.1251del (p.Ser418fs) also known as (p.Ser418AlafsTer12) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 12/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). To our knowledge, this variant has not been reported in the literature in any individuals with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency. Additionally, to our knowledge, functional assays have not been reported for this variant. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Supporting (VCEP specifications version1; approved November 8, 2021)

Met criteria codes

• PM2_Supporting: This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
• PVS1: The c.1251del (p.Ser418AlafsTer12) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 12/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).