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.623-1G>A

CA397723333

811525 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 8ce67693-5017-4b9e-82a1-8bde4b694a06
Approved on: 2023-06-27
Published on: 2023-06-27

HGVS expressions

NM_000018.4:c.623-1G>A
NM_000018.4(ACADVL):c.623-1G>A
NC_000017.11:g.7221951G>A
CM000679.2:g.7221951G>A
NC_000017.10:g.7125270G>A
CM000679.1:g.7125270G>A
NC_000017.9:g.7065994G>A
NG_007975.1:g.7118G>A
NG_008391.2:g.3100C>T
ENST00000356839.10:c.623-1G>A
ENST00000322910.9:c.*578-1G>A
ENST00000350303.9:c.557-1G>A
ENST00000356839.9:c.623-1G>A
ENST00000543245.6:c.692-1G>A
ENST00000577191.5:n.700-1G>A
ENST00000577857.5:n.439-1G>A
ENST00000579286.5:n.804-1G>A
ENST00000579886.2:c.461-1G>A
ENST00000580365.1:n.354-1G>A
ENST00000581378.5:n.341-1G>A
ENST00000581562.5:n.525-1G>A
ENST00000582379.1:n.6G>A
ENST00000583312.5:c.637G>A
ENST00000583760.1:n.405-1G>A
NM_000018.3:c.623-1G>A
NM_001033859.2:c.557-1G>A
NM_001270447.1:c.692-1G>A
NM_001270448.1:c.395-1G>A
NM_001033859.3:c.557-1G>A
NM_001270447.2:c.692-1G>A
NM_001270448.2:c.395-1G>A

Likely Pathogenic

Met criteria codes 2
PM2_Supporting PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The NM_000018.4(ACADVL):c.623-1G>A variant in ACADVL occurs within the canonical splice acceptor site (-1) of intron 7. It is predicted to cause skipping of biologically-relevant-exon 8, resulting in a frameshift 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) and reported in an infant patient with dilated cardiomyopathy/sudden death, co-identified with c.932del; p.Phe311Serfs*42 in trans (PMID: 10077518). Although computational splicing predictor SpliceAI gives a score of 0.92 for acceptor loss, predicting that the variant disrupts the acceptor splice site of intron 7 of ACADVL, PP3 is not applicable since this evidence is already weighed in PVS1. 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_Supporting.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1.
PVS1
The NM_000018.4(ACADVL):c.623-1G>A variant in ACADVL occurs within the canonical splice acceptor site (-1) of intron 7. It is predicted to cause skipping of biologically-relevant-exon 8, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).
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