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]

Variant: NM_000018.4(ACADVL):c.1251del (p.Ser418fs)

CA2499224903

1073505 (ClinVar)

Gene: ACADVL (HGNC:37)

Condition: very long chain acyl-CoA dehydrogenase deficiency (MONDO:0008723)

Inheritance Mode: Autosomal recessive inheritance

UUID: ed709b5f-bc3d-4070-a616-dfde5be00520

Approved on: 2022-12-14

Published on: 2022-12-14

HGVS expressions

NM_000018.4:c.1251del

NM_000018.4(ACADVL):c.1251del (p.Ser418fs)

NC_000017.11:g.7223712del

CM000679.2:g.7223712del

NC_000017.10:g.7127031del

CM000679.1:g.7127031del

NC_000017.9:g.7067755del

NG_007975.1:g.8879del

NG_008391.2:g.1339del

NG_033038.1:g.15833del

ENST00000356839.10:c.1251del

ENST00000322910.9:c.*1206del

ENST00000350303.9:c.1185del

ENST00000356839.9:c.1251del

ENST00000542255.6:n.109del

ENST00000543245.6:c.1320del

ENST00000578579.2:n.422del

ENST00000578711.1:n.208del

ENST00000578824.5:n.667del

ENST00000579425.5:n.275del

ENST00000579546.1:n.88del

ENST00000583850.5:n.26del

ENST00000583858.5:n.280del

ENST00000585203.6:n.459del

NM_000018.3:c.1251del

NM_001033859.2:c.1185del

NM_001270447.1:c.1320del

NM_001270448.1:c.1023del

NM_001033859.3:c.1185del

NM_001270447.2:c.1320del

NM_001270448.2:c.1023del

Likely Pathogenic

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

PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1251del (p.Ser418fs) also known as (p.Ser418AlafsTer12) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 12/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). To our knowledge, this variant has not been reported in the literature in any individuals with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency. Additionally, to our knowledge, functional assays have not been reported for this variant. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Supporting (VCEP specifications version1; approved November 8, 2021)

PVS1

The c.1251del (p.Ser418AlafsTer12) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 12/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

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.