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]
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Variant: NM_000018.3(ACADVL):c.1375dup

CA312288

203592 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 8b8497f6-f174-4d15-8e5d-eb9e874a6d80
Approved on: 2022-12-14
Published on: 2022-12-14

HGVS expressions

NM_000018.3:c.1375dupC
NM_000018.3(ACADVL):c.1375dup
NC_000017.11:g.7224010dup
CM000679.2:g.7224010dup
NC_000017.10:g.7127329dup
CM000679.1:g.7127329dup
NC_000017.9:g.7068053dup
NG_007975.1:g.9177dup
NG_008391.2:g.1042dup
NG_033038.1:g.15536dup
ENST00000356839.10:c.1375dup
ENST00000322910.9:c.*1330dup
ENST00000350303.9:c.1309dup
ENST00000356839.9:c.1375dup
ENST00000542255.6:n.233dup
ENST00000543245.6:c.1444dup
ENST00000578711.1:n.506dup
ENST00000579425.5:n.491dup
ENST00000579546.1:n.212dup
ENST00000579894.5:n.86dup
ENST00000583074.5:n.94dup
ENST00000583850.5:n.150dup
ENST00000583858.5:n.404dup
ENST00000585203.6:n.566dup
NM_000018.3:c.1375dup
NM_001033859.2:c.1309dup
NM_001270447.1:c.1444dup
NM_001270448.1:c.1147dup
NM_000018.4:c.1375dup
NM_001033859.3:c.1309dup
NM_001270447.2:c.1444dup
NM_001270448.2:c.1147dup
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Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 2
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.1375dup (p.Arg459ProfsTer4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon14/20 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 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 0.000008794 in the European (non-Finnish) 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 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)
Met criteria codes
PVS1
The c.1375dup (p.Arg459ProfsTer4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon14/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124).
PM2_Supporting
The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008794 in the European (non-Finnish) population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).
Curation History
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