Variant: NM_000018.4(ACADVL):c.1508del (p.Gly503fs)

CA624860719

839947 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 38b303c0-41f2-42dd-acc1-709b4e13b1e2

Approved on: 2022-12-14

Published on: 2022-12-14

HGVS expressions

NM_000018.4:c.1508del
NM_000018.4(ACADVL):c.1508del (p.Gly503fs)
NC_000017.11:g.7224219del
CM000679.2:g.7224219del
NC_000017.10:g.7127538del
CM000679.1:g.7127538del
NC_000017.9:g.7068262del
NG_007975.1:g.9386del
NG_008391.2:g.833del
NG_033038.1:g.15327del
ENST00000356839.10:c.1508del
ENST00000322910.9:c.*1463del
ENST00000350303.9:c.1442del
ENST00000356839.9:c.1508del
ENST00000542255.6:n.366del
ENST00000543245.6:c.1577del
ENST00000578319.5:n.3del
ENST00000578711.1:n.715del
ENST00000578809.5:n.3del
ENST00000579391.1:n.116del
ENST00000579425.5:n.624del
ENST00000579546.1:n.272-102del
ENST00000579894.5:n.295del
ENST00000583074.5:n.154-102del
ENST00000583850.5:n.283del
ENST00000583858.5:n.464-102del
ENST00000585203.6:n.699del
NM_000018.3:c.1508del
NM_001033859.2:c.1442del
NM_001270447.1:c.1577del
NM_001270448.1:c.1280del
NM_001033859.3:c.1442del
NM_001270447.2:c.1577del
NM_001270448.2:c.1280del

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.1508del (p.Gly503fs) variant in ACADVL, also known as p.Gly503GlufsTer7, is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 15/20 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 0.000008796 in the 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). 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 version 1; approved November 8, 2021

Met criteria codes

• PM2_Supporting: The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008796 in the 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.1508del (p.Gly503fs) variant in ACADVL, also known as p.Gly503GlufsTer7, is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 15/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).