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

CA8337657

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: d7273f17-2641-49cc-b8a0-6066c39103c0

Approved on: 2022-09-23

Published on: 2022-09-23

HGVS expressions

NM_000018.4:c.342+1G>A

NC_000017.11:g.7220831G>A

CM000679.2:g.7220831G>A

NC_000017.10:g.7124150G>A

CM000679.1:g.7124150G>A

NC_000017.9:g.7064874G>A

NG_007975.1:g.5998G>A

NG_008391.2:g.4220C>T

ENST00000356839.10:c.342+1G>A

ENST00000322910.9:c.*297+1G>A

ENST00000350303.9:c.276+1G>A

ENST00000356839.9:c.342+1G>A

ENST00000543245.6:c.411+1G>A

ENST00000577191.5:n.419+1G>A

ENST00000577433.5:n.550+1G>A

ENST00000577857.5:n.293+1G>A

ENST00000579286.5:n.523+1G>A

ENST00000579886.2:c.202-114G>A

ENST00000580365.1:n.73+1G>A

ENST00000581378.5:n.41+1G>A

ENST00000581562.5:n.389+1G>A

ENST00000582056.5:n.433G>A

ENST00000582166.1:n.231G>A

ENST00000582356.5:n.542G>A

ENST00000583312.5:c.342+1G>A

ENST00000584103.5:c.342+1G>A

NM_000018.3:c.342+1G>A

NM_001033859.2:c.276+1G>A

NM_001270447.1:c.411+1G>A

NM_001270448.1:c.114+1G>A

NM_001033859.3:c.276+1G>A

NM_001270447.2:c.411+1G>A

NM_001270448.2:c.114+1G>A

Likely Pathogenic

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

PM2_Supporting PVS1

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.342+1G>A variant in ACADVL is a splice site variant affecting the canonical donor splice site in intron 5. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present at low frequency (<0.1%) in population databases (ExAC). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site (Splice AI). This variant has not been reported in the literature either in functional studies or in patients with VLCAD and there is no entry in ClinVar. This variant is classified as Likely Pathogenic based on ACADVL-specific ACMG/AMP criteria PVS1 and PM2.

PM2_Supporting

MAF <0.001 in population databases

PVS1

c.342+1G>A affects a canonical donor splice site in intron 5 which is predicted to disrupt splicing causing the skipping of exon 5 which would lead to a premature stop codon. Splice AI predicts a donor site loss with a score of 1.0.

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