Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_000018.4(ACADVL):c.37C>T (p.Gln13Ter)

CA287433650

812785 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 9092ac6d-ee1f-4776-967f-41c813d5ca66
Approved on: 2022-12-14
Published on: 2022-12-14

HGVS expressions

NM_000018.4:c.37C>T
NM_000018.4(ACADVL):c.37C>T (p.Gln13Ter)
NC_000017.11:g.7220021C>T
CM000679.2:g.7220021C>T
NC_000017.10:g.7123340C>T
CM000679.1:g.7123340C>T
NC_000017.9:g.7064064C>T
NG_007975.1:g.5188C>T
NG_008391.2:g.5030G>A
ENST00000356839.10:c.37C>T
ENST00000322910.9:c.37C>T
ENST00000350303.9:c.37C>T
ENST00000356839.9:c.37C>T
ENST00000543245.6:c.132-101C>T
ENST00000577191.5:n.114C>T
ENST00000577857.5:n.127C>T
ENST00000578269.5:n.144C>T
ENST00000578421.1:n.96C>T
ENST00000579286.5:n.144C>T
ENST00000579886.2:c.37C>T
ENST00000580263.5:n.127C>T
ENST00000581562.5:n.84C>T
ENST00000582056.5:n.127C>T
ENST00000582356.5:n.162C>T
ENST00000583312.5:c.37C>T
ENST00000584103.5:c.37C>T
NM_000018.3:c.37C>T
NM_001033859.2:c.37C>T
NM_001270447.1:c.132-101C>T
NM_001270448.1:c.-267C>T
NM_001365.3:c.-1172G>A
NM_001321074.1:c.-1172G>A
NM_001365.4:c.-1172G>A
NR_135527.1:n.30G>A
NM_001033859.3:c.37C>T
NM_001270447.2:c.132-101C>T
NM_001270448.2:c.-267C>T
More

Pathogenic

Met criteria codes 3
PP4_Moderate PVS1 PM2_Supporting
Not Met criteria codes 7
BS1 BP1 PS1 BA1 PP2 PM1 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.37C>T (p.Gln13Ter) variant in ACADVL is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 1/20 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 patient with this variant displayed VLCAD enzyme levels of <20% of normal, which is highly specific for very long chain acyl CoA dehydrogenase (VLCAD) deficiency (PP4_Moderate; PMIDs: 20060901, 17999356). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PP4_Moderate, PM2_Supporting (ACADVL VCEP specifications version 1; approved November 8, 2021).
Met criteria codes
PP4_Moderate
Detected in patient with <20% VLCAD activity (PMID: 20060901, 17999356)
PVS1
The nonsense variant is expected to result in LOF, which is a known mechanism of disease for ACADVL. The next in frame methionine is at codon 77.
PM2_Supporting
Variant was not found in gnomAD. Used PM2_Supporting based on SVI guidance.
Not Met criteria codes
BS1
Variant was not found in gnomAD
BP1
Not a missense variant
PS1
No other nonsense change was found for codon 13.
BA1
Variant was not found in gnomAD
PP2
Not a missense variant
PM1
Amino acid 13 is not located in a mutational hotspot
PM5
The variant is nonsense, not missense
Curation History
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