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.1316del (p.Gly439fs)

CA8338063

932852 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 70dff852-cf27-44e2-8b9e-f0297921e46c

HGVS expressions

NM_000018.4:c.1316del

NM_000018.4(ACADVL):c.1316del (p.Gly439fs)

NC_000017.11:g.7223859del

CM000679.2:g.7223859del

NC_000017.10:g.7127178del

CM000679.1:g.7127178del

NC_000017.9:g.7067902del

NG_007975.1:g.9026del

NG_008391.2:g.1197del

NG_033038.1:g.15691del

ENST00000356839.10:c.1316del

ENST00000322910.9:c.*1271del

ENST00000350303.9:c.1250del

ENST00000356839.9:c.1316del

ENST00000542255.6:n.174del

ENST00000543245.6:c.1385del

ENST00000578711.1:n.355del

ENST00000579425.5:n.340del

ENST00000579546.1:n.153del

ENST00000583074.5:n.35del

ENST00000583850.5:n.91del

ENST00000583858.5:n.345del

ENST00000585203.6:n.523+1del

NM_000018.3:c.1316del

NM_001033859.2:c.1250del

NM_001270447.1:c.1385del

NM_001270448.1:c.1088del

NM_001033859.3:c.1250del

NM_001270447.2:c.1385del

NM_001270448.2:c.1088del

Likely Pathogenic

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

PVS1 PM2_Supporting

PP4

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4(ACADVL); c.1316del(p.Gly439Valfs*5) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 13 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 individual with this variant was identified by newborn screen, but this information is insufficient for to use toward classification (PMID: 26385305). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003 in South Asian 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 likely 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, PM2_Supporting.

PVS1

PM2_Supporting

). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003 in South Asian population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).

PP4

At least one individual with this variant was identified by newborn screen, but this information is insufficient for to use toward classification (PMID: 26385305).

Approved on: 2023-03-27

Published on: 2023-03-27

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