The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_000018.4(ACADVL):c.63-2A>C

CA397722016

474900 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
UUID: 5c62664a-7354-47c7-87a8-0b26feb8a5b9
Approved on: 2022-03-08
Published on: 2022-03-08

HGVS expressions

NM_000018.4:c.63-2A>C
NM_000018.4(ACADVL):c.63-2A>C
NC_000017.11:g.7220120A>C
CM000679.2:g.7220120A>C
NC_000017.10:g.7123439A>C
CM000679.1:g.7123439A>C
NC_000017.9:g.7064163A>C
NG_007975.1:g.5287A>C
NG_008391.2:g.4931T>G
ENST00000356839.10:c.63-2A>C
ENST00000322910.9:c.*16A>C
ENST00000350303.9:c.63-2A>C
ENST00000356839.9:c.63-2A>C
ENST00000543245.6:c.132-2A>C
ENST00000577191.5:n.140-2A>C
ENST00000577857.5:n.153-2A>C
ENST00000578269.5:n.170-2A>C
ENST00000578421.1:n.195A>C
ENST00000579286.5:n.170-2A>C
ENST00000579886.2:c.63-2A>C
ENST00000580263.5:n.153-2A>C
ENST00000581562.5:n.110-2A>C
ENST00000582056.5:n.153-2A>C
ENST00000582356.5:n.188-2A>C
ENST00000583312.5:c.63-2A>C
ENST00000584103.5:c.63-2A>C
NM_000018.3:c.63-2A>C
NM_001033859.2:c.63-2A>C
NM_001270447.1:c.132-2A>C
NM_001270448.1:c.-168A>C
NM_001033859.3:c.63-2A>C
NM_001270447.2:c.132-2A>C
NM_001270448.2:c.-168A>C
More

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 2
PVS1 PM2_Supporting
Not Met criteria codes 2
PM3 PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.63-2A>C variant in ACADVL occurs within the canonical splice acceptor site (+/- 1,2) of intron 1. It is predicted to cause skipping of biologically-relevant-exon 2/20, 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). This variant has been reported in an abnormal newborn screen without clinical confirmation or a second pathogenic ACADVL variant identified (PMID 26385305, 27209629). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting (VCEP specifications v2.0, approved on 09/16/2021).
Met criteria codes
PVS1
c.63-2A>C affects canonical acceptor splice site in intron 1 which is predicted to disrupt splicing causing the skipping of exon 2, which would lead to frameshift, premature stop codon, and NMD.
PM2_Supporting
This variant is absent from population database (gnomAD) meeting PM2_supporting
Not Met criteria codes
PM3
The second variant is benign with 1% MAF in gnomad
PP4
Clinical information and confirmatory study not provided. A second potential disease causing variant not identified.
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.