NM_000018.4:c.856_857del

932846 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: a960d8de-725c-4f8c-aff8-1a7c6c426f68

Approved on: 2023-09-26

Published on: 2023-09-26

HGVS expressions

NM_000018.4:c.856_857del
NM_000018.4(ACADVL):c.856_857del (p.Arg286fs)

Likely Pathogenic

• Met criteria codes: PM2_Supporting PVS1

• Not Met criteria codes: PP4

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The c.856_857del (p.Arg286fs)(NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 9/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). At least one individual with this variant was identified by newborn screen, but this information is insufficient to use toward classification (PMID: 26385305). 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_Suporting (ACADVL VCEP specifications version 1; approved November 9, 2021).

Met criteria codes

• PM2_Supporting: This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
• PVS1: The c.856_857del (p.Arg286fs)(NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 9/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).

Not Met criteria codes

• PP4: At least one individual with this variant was identified by newborn screen, but this information is insufficient to use toward classification (PMID: 26385305).