Variant: NM_000018.4(ACADVL):c.316_325del (p.Val106fs)

CA16043042

373614 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 12144d96-58b0-4b96-86ce-031a6bd2ac80

Approved on: 2022-12-14

Published on: 2022-12-14

HGVS expressions

NM_000018.4:c.316_325del
NM_000018.4(ACADVL):c.316_325del (p.Val106fs)
NC_000017.11:g.7220804_7220813del
CM000679.2:g.7220804_7220813del
NC_000017.10:g.7124123_7124132del
CM000679.1:g.7124123_7124132del
NC_000017.9:g.7064847_7064856del
NG_007975.1:g.5971_5980del
NG_008391.2:g.4241_4250del
ENST00000356839.10:c.316_325del
ENST00000322910.9:c.*271_*280del
ENST00000350303.9:c.250_259del
ENST00000356839.9:c.316_325del
ENST00000543245.6:c.385_394del
ENST00000577191.5:n.393_402del
ENST00000577433.5:n.524_533del
ENST00000577857.5:n.267_276del
ENST00000579286.5:n.497_506del
ENST00000579886.2:c.202-141_202-132del
ENST00000580365.1:n.47_56del
ENST00000581378.5:n.15_24del
ENST00000581562.5:n.363_372del
ENST00000582056.5:n.406_415del
ENST00000582166.1:n.204_213del
ENST00000582356.5:n.515_524del
ENST00000583312.5:c.316_325del
ENST00000584103.5:c.316_325del
NM_000018.3:c.316_325del
NM_001033859.2:c.250_259del
NM_001270447.1:c.385_394del
NM_001270448.1:c.88_97del
NM_001033859.3:c.250_259del
NM_001270447.2:c.385_394del
NM_001270448.2:c.88_97del

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.316_325del (p.Val106Cysfs*8) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 5/20 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, this variant has not been reported in the literature in any individuals with VLCADD. To our knowledge, functional assays have not been reported for this variant. In summary, this variant has been 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 ACADVL Expert Panel: PVS1, PM2_Supporting (ClinGen ACADVL VCEP specifications version#2.0; approved 05-09-22).

Met criteria codes

• PM2_Supporting: PM2_Supporting is met. This variant is absent from gnomAD 2.1.1 (PM2_Supporting).
• PVS1: PVS1 is met. The c.316_325del (p.Val106Cysfs*8) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 5/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs: 9973285, 11590124).