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.1630_1645del (p.Ala544fs)

CA624860771

429730 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6857e477-aa3e-4a02-8112-e637a6bd27cf

Approved on: 2022-12-15

Published on: 2022-12-15

HGVS expressions

NM_000018.4:c.1630_1645del

NM_000018.4(ACADVL):c.1630_1645del (p.Ala544fs)

NC_000017.11:g.7224504_7224519del

CM000679.2:g.7224504_7224519del

NC_000017.10:g.7127823_7127838del

CM000679.1:g.7127823_7127838del

NC_000017.9:g.7068547_7068562del

NG_007975.1:g.9671_9686del

NG_008391.2:g.532_547del

NG_033038.1:g.15026_15041del

ENST00000356839.10:c.1630_1645del

ENST00000322910.9:c.*1585_*1600del

ENST00000350303.9:c.1564_1579del

ENST00000356839.9:c.1630_1645del

ENST00000542255.6:n.488_503del

ENST00000543245.6:c.1699_1714del

ENST00000578319.5:n.211_226del

ENST00000578711.1:n.1000_1015del

ENST00000578809.5:n.202_217del

ENST00000579391.1:n.234_249del

ENST00000579425.5:n.746_761del

ENST00000579546.1:n.365_380del

ENST00000582450.1:n.138_153del

ENST00000583074.5:n.251_266del

ENST00000583848.5:n.16_31del

ENST00000583850.5:n.401_416del

ENST00000583858.5:n.561_576del

ENST00000585203.6:n.821_836del

NM_000018.3:c.1630_1645del

NM_001033859.2:c.1564_1579del

NM_001270447.1:c.1699_1714del

NM_001270448.1:c.1402_1417del

NM_001033859.3:c.1564_1579del

NM_001270447.2:c.1699_1714del

NM_001270448.2:c.1402_1417del

Likely Pathogenic

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

PM2_Supporting PVS1

PP4

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1630_1645del (p.Ala544Profs*3) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 17/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003 in the South Asian population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in any individuals with VLCADD. The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting.

PM2_Supporting

gnomAD 0.00003 in South Asian: lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting

PVS1

Frameshift in exon 17/20

PP4

Reported in a carrier screening at risk for an affected pregnancy study (PMID: 29760218). No mention of VLCADD

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