Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000018.4(ACADVL):c.1283del (p.Lys428fs)

CA658824843

557078 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b2328cc2-a9d9-4aa6-9726-4ca76dbc14c0

HGVS expressions

NM_000018.4:c.1283del

NM_000018.4(ACADVL):c.1283del (p.Lys428fs)

NC_000017.11:g.7223826del

CM000679.2:g.7223826del

NC_000017.10:g.7127145del

CM000679.1:g.7127145del

NC_000017.9:g.7067869del

NG_007975.1:g.8993del

NG_008391.2:g.1226del

NG_033038.1:g.15720del

ENST00000356839.10:c.1283del

ENST00000322910.9:c.*1238del

ENST00000350303.9:c.1217del

ENST00000356839.9:c.1283del

ENST00000542255.6:n.141del

ENST00000543245.6:c.1352del

ENST00000578579.2:n.454del

ENST00000578711.1:n.322del

ENST00000578824.5:n.699del

ENST00000579425.5:n.307del

ENST00000579546.1:n.120del

ENST00000583074.5:n.2del

ENST00000583850.5:n.58del

ENST00000583858.5:n.312del

ENST00000585203.6:n.491del

NM_000018.3:c.1283del

NM_001033859.2:c.1217del

NM_001270447.1:c.1352del

NM_001270448.1:c.1055del

NM_001033859.3:c.1217del

NM_001270447.2:c.1352del

NM_001270448.2:c.1055del

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4(ACADVL);c.1283del(p.Lys428Argfs*2) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 13 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 v2.1.1 (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

PVS1

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

Approved on: 2022-12-15

Published on: 2022-12-15

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.