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.1409del (p.Leu470fs)

CA1139665152

938242 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4e57b5cd-cf40-49c5-b6f3-ed05ff653615

HGVS expressions

NM_000018.4:c.1409del

NM_000018.4(ACADVL):c.1409del (p.Leu470fs)

NC_000017.11:g.7224044del

CM000679.2:g.7224044del

NC_000017.10:g.7127363del

CM000679.1:g.7127363del

NC_000017.9:g.7068087del

NG_007975.1:g.9211del

NG_008391.2:g.1007del

NG_033038.1:g.15501del

ENST00000356839.10:c.1409del

ENST00000322910.9:c.*1364del

ENST00000350303.9:c.1343del

ENST00000356839.9:c.1409del

ENST00000542255.6:n.267del

ENST00000543245.6:c.1478del

ENST00000578711.1:n.540del

ENST00000579425.5:n.525del

ENST00000579546.1:n.246del

ENST00000579894.5:n.120del

ENST00000583074.5:n.128del

ENST00000583850.5:n.184del

ENST00000583858.5:n.438del

ENST00000585203.6:n.600del

NM_000018.3:c.1409del

NM_001033859.2:c.1343del

NM_001270447.1:c.1478del

NM_001270448.1:c.1181del

NM_001033859.3:c.1343del

NM_001270447.2:c.1478del

NM_001270448.2:c.1181del

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 Specification: ClinGen ACADVL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1409del (p.Leu470Argfs*22) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 14/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9328975, 11590124). 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. PM2_Supporting is met. 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, (ClinGen ACADVL VCEP specifications version#1.0; approved 08-08-22).

PVS1

PVS1 is met. The c.1409del (p.Leu470Argfs*22) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 14/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124).

PM2_Supporting

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

Approved on: 2022-09-13

Published on: 2022-09-13

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