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.1077+1G>A

CA287437693

448981 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 2020afa6-e23a-48b8-be9f-38d8a6964d30

Approved on: 2022-07-12

Published on: 2022-07-12

HGVS expressions

NM_000018.4:c.1077+1G>A

NM_000018.4(ACADVL):c.1077+1G>A

NC_000017.11:g.7222866G>A

CM000679.2:g.7222866G>A

NC_000017.10:g.7126185G>A

CM000679.1:g.7126185G>A

NC_000017.9:g.7066909G>A

NG_007975.1:g.8033G>A

NG_008391.2:g.2185C>T

ENST00000356839.10:c.1077+1G>A

ENST00000322910.9:c.*1032+1G>A

ENST00000350303.9:c.1011+1G>A

ENST00000356839.9:c.1077+1G>A

ENST00000543245.6:c.1146+1G>A

ENST00000578824.5:n.227G>A

ENST00000582379.1:n.462G>A

ENST00000583858.5:n.106+1G>A

ENST00000585203.6:n.19G>A

NM_000018.3:c.1077+1G>A

NM_001033859.2:c.1011+1G>A

NM_001270447.1:c.1146+1G>A

NM_001270448.1:c.849+1G>A

NM_001033859.3:c.1011+1G>A

NM_001270447.2:c.1146+1G>A

NM_001270448.2:c.849+1G>A

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.1077+1G>A variant in ACADVL occurs within the canonical splice donor site of intron 10. It is predicted to cause skipping of biologically-relevant-exon 10, 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). The highest population minor allele frequency in gnomAD is 0.00006 in the African population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) meeting this criterion (PM2_Supporting). This variant has been reported once as a heterozygote associated with very-long chain acyl-CoA dehydrogenase deficiency (PMID: 26385305). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting.

PM2_Supporting

2 alleles in gnomAD MAF<0.001

PVS1

Donor splice site of intron 10

PP4

1 heterozygote patient with VLCADD

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