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.602A>G (p.Tyr201Cys)

CA397723258

932789 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: d1956c84-3f68-4c7c-a275-d88ca90be85b

HGVS expressions

NM_000018.4:c.602A>G

NM_000018.4(ACADVL):c.602A>G (p.Tyr201Cys)

NC_000017.11:g.7221662A>G

CM000679.2:g.7221662A>G

NC_000017.10:g.7124981A>G

CM000679.1:g.7124981A>G

NC_000017.9:g.7065705A>G

NG_007975.1:g.6829A>G

NG_008391.2:g.3389T>C

ENST00000356839.10:c.602A>G

ENST00000322910.9:c.*557A>G

ENST00000350303.9:c.536A>G

ENST00000356839.9:c.602A>G

ENST00000543245.6:c.671A>G

ENST00000577191.5:n.679A>G

ENST00000577857.5:n.418A>G

ENST00000579286.5:n.783A>G

ENST00000579886.2:c.440A>G

ENST00000580365.1:n.333A>G

ENST00000581378.5:c.320A>G

ENST00000581562.5:n.525-290A>G

ENST00000583312.5:c.602A>G

ENST00000583760.1:n.384A>G

NM_000018.3:c.602A>G

NM_001033859.2:c.536A>G

NM_001270447.1:c.671A>G

NM_001270448.1:c.374A>G

NM_001033859.3:c.536A>G

NM_001270447.2:c.671A>G

NM_001270448.2:c.374A>G

Likely Pathogenic

PM3_Supporting PM2_Supporting PP1 PP3 PP4_Moderate

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.602A>G (NM_000018.4) variant in ACADVL is a missense variant predicted to cause substitution of tyrosine by cysteine at amino acid 201 (p.Tyr201Cys). This variant has been detected in a set of siblings that displayed increased C14:1 on newborn screen and reduced very long chain acyl CoA dehydrogenase (VLCAD) enzyme activity, which is highly specific for VLCAD deficiency (PP4_moderate, PP1; PMID: 17457695, 14517516). These siblings were compound heterozygous for this variant and a likely pathogenic variant confirmed in trans by parental testing (PM3 0.5 points, PM3_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.954, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM2_Supporting, PM3_Supporting, PP1, PP3, PP4_Moderate (ACADVL VCEP specifications version 1; approved November 9, 2021

PM3_Supporting

Detected confirmed in trans to A490P in 2 siblings.

PM2_Supporting

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

PP1

2 affected siblings from one family

PP3

The computational predictor REVEL gives a score of 0.954, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3).

PP4_Moderate

increased C14:1 on newborn screen and reduced very long chain acyl CoA dehydrogenase (VLCAD) enzyme activity

Approved on: 2023-11-28

Published on: 2023-11-28

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