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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computer assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000018.4(ACADVL):c.956C>A (p.Ser319Ter)

CA8337912

557676 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 9ddd44b9-b03b-41f5-89a3-9356428a1807
Approved on: 2024-05-14
Published on: 2024-05-16

HGVS expressions

NM_000018.4:c.956C>A
NM_000018.4(ACADVL):c.956C>A (p.Ser319Ter)
NC_000017.11:g.7222744C>A
CM000679.2:g.7222744C>A
NC_000017.10:g.7126063C>A
CM000679.1:g.7126063C>A
NC_000017.9:g.7066787C>A
NG_007975.1:g.7911C>A
NG_008391.2:g.2307G>T
ENST00000356839.10:c.956C>A
ENST00000322910.9:c.*911C>A
ENST00000350303.9:c.890C>A
ENST00000356839.9:c.956C>A
ENST00000543245.6:c.1025C>A
ENST00000578824.5:n.105C>A
ENST00000581378.5:c.674C>A
ENST00000582379.1:n.340C>A
NM_000018.3:c.956C>A
NM_001033859.2:c.890C>A
NM_001270447.1:c.1025C>A
NM_001270448.1:c.728C>A
NM_001033859.3:c.890C>A
NM_001270447.2:c.1025C>A
NM_001270448.2:c.728C>A
More

Pathogenic

Met criteria codes 3
PP4 PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.956C>A (p.Ser319Ter)(NM_000018.3) variant in ACADVL is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 10/20 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 NBS and follow-up data, which is highly specific for VLCAD deficiency (PP4_supporting, PMID: 27209629). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006 in the African population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as 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, PP4_supporting, PM2_supporting (ACADVL VCEP specifications version 1; approved November 9, 2021).
Met criteria codes
PP4
NBS C14:1 Levels from >0.8 μM
PVS1
Premature stop codon exon 10 of 20.
PM2_Supporting
gnomAD v2.1.1 is 0.00006 in the African population
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.