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.565_587del (p.Ile189fs)

CA624860664

856881 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 8bb78386-8278-49a2-8788-c956a8ae7675

HGVS expressions

NM_000018.4:c.565_587del

NM_000018.4(ACADVL):c.565_587del (p.Ile189fs)

NC_000017.11:g.7221625_7221647del

CM000679.2:g.7221625_7221647del

NC_000017.10:g.7124944_7124966del

CM000679.1:g.7124944_7124966del

NC_000017.9:g.7065668_7065690del

NG_007975.1:g.6792_6814del

NG_008391.2:g.3411_3433del

ENST00000356839.10:c.565_587del

ENST00000322910.9:c.*520_*542del

ENST00000350303.9:c.499_521del

ENST00000356839.9:c.565_587del

ENST00000543245.6:c.634_656del

ENST00000577191.5:n.642_664del

ENST00000577433.5:n.773_795del

ENST00000577857.5:n.381_403del

ENST00000579286.5:n.746_768del

ENST00000579886.2:c.403_425del

ENST00000580365.1:n.296_318del

ENST00000581378.5:n.283_305del

ENST00000581562.5:n.525-327_525-305del

ENST00000583312.5:c.565_587del

ENST00000583760.1:n.347_369del

NM_000018.3:c.565_587del

NM_001033859.2:c.499_521del

NM_001270447.1:c.634_656del

NM_001270448.1:c.337_359del

NM_001033859.3:c.499_521del

NM_001270447.2:c.634_656del

NM_001270448.2:c.337_359del

Likely Pathogenic

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

PM2_Supporting PVS1

PP4

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.565_587del (p.Ile189fs) 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). This variant is absent from gnomAD v2.1.1 (PM2_supporting). This variant was found in an individual identified via newborn screening, however no second variant was detected. Residual VLCAD enzyme activity was 34% of normal. Therefore this proband is not considered in this clarification (PMID 21932095). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting. VCEP specifications version 1; 11/8/21).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_supporting)

PVS1

PP4

This variant was found in an individual identified via newborn screening, however no second variant was detected. Residual VLCAD enzyme activity was 34% of normal. PMID 21932095.

Approved on: 2022-09-20

Published on: 2022-09-20

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