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.652_682dup (p.Ile228fs)

CA8337802

581080 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: eb7fde51-c627-4c18-93d8-c6bbfb1df4b0

HGVS expressions

NM_000018.4:c.652_682dup

NM_000018.4(ACADVL):c.652_682dup (p.Ile228fs)

NC_000017.11:g.7221981_7222011dup

CM000679.2:g.7221981_7222011dup

NC_000017.10:g.7125300_7125330dup

CM000679.1:g.7125300_7125330dup

NC_000017.9:g.7066024_7066054dup

NG_007975.1:g.7148_7178dup

NG_008391.2:g.3040_3070dup

ENST00000356839.10:c.652_682dup

ENST00000322910.9:c.*607_*637dup

ENST00000350303.9:c.586_616dup

ENST00000356839.9:c.652_682dup

ENST00000543245.6:c.721_751dup

ENST00000577191.5:n.729_759dup

ENST00000577857.5:n.468_498dup

ENST00000579286.5:n.833_863dup

ENST00000580365.1:n.383_413dup

ENST00000581378.5:n.370_400dup

ENST00000582379.1:n.36_66dup

ENST00000583760.1:n.434_464dup

NM_000018.3:c.652_682dup

NM_001033859.2:c.586_616dup

NM_001270447.1:c.721_751dup

NM_001270448.1:c.424_454dup

NM_001033859.3:c.586_616dup

NM_001270447.2:c.721_751dup

NM_001270448.2:c.424_454dup

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 c.652_682dup (p.Ile228ArgfsTer35) variant in ACADVL is a nonsense 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). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+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: PM2_supporting, PVS1 (ACADVL VCEP specifications version 1; approved November 8, 2021).

PVS1

PM2_Supporting

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

Approved on: 2022-12-14

Published on: 2022-12-14

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