Variant: NM_000018.4(ACADVL):c.497_498del (p.Ile166fs)

CA16041861

370277 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: b7a14752-55ee-4ba8-9a0f-264fde493683

Approved on: 2022-05-22

Published on: 2022-05-22

HGVS expressions

NM_000018.4:c.497_498del
NM_000018.4(ACADVL):c.497_498del (p.Ile166fs)
NC_000017.11:g.7221557_7221558del
CM000679.2:g.7221557_7221558del
NC_000017.10:g.7124876_7124877del
CM000679.1:g.7124876_7124877del
NC_000017.9:g.7065600_7065601del
NG_007975.1:g.6724_6725del
NG_008391.2:g.3493_3494del
ENST00000356839.10:c.497_498del
ENST00000322910.9:c.*452_*453del
ENST00000350303.9:c.431_432del
ENST00000356839.9:c.497_498del
ENST00000543245.6:c.566_567del
ENST00000577191.5:n.574_575del
ENST00000577433.5:n.705_706del
ENST00000577857.5:n.313_314del
ENST00000579286.5:n.678_679del
ENST00000579886.2:c.335_336del
ENST00000580365.1:n.228_229del
ENST00000581378.5:n.215_216del
ENST00000581562.5:n.525-395_525-394del
ENST00000582166.1:n.478_479del
ENST00000583312.5:c.497_498del
ENST00000583760.1:n.279_280del
NM_000018.3:c.497_498del
NM_001033859.2:c.431_432del
NM_001270447.1:c.566_567del
NM_001270448.1:c.269_270del
NM_001033859.3:c.431_432del
NM_001270447.2:c.566_567del
NM_001270448.2:c.269_270del

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.497_498del (p.Ile166SerfsTer5) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 7/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00001 in European (Non-Finnish) population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). To our knowledge, this variant has not been reported in the literature either in a patient with VLCAD or ACADVL associated disease or in functional studies. 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. The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting. VCEP specifications version 2; 10/15/21.

Met criteria codes

• PM2_Supporting: The highest population minor allele frequency in gnomAD v2.1.1 is 0.00001 in European (Non-Finnish) population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).
• PVS1: The c.497_498del (p.Ile166SerfsTer5) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 7/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).