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]

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Variant: NM_001270448.2:c.1599+1G>A

CA397725976

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3fe7fd31-6941-4341-a68d-857d4c4c3ab5

Approved on: 2024-04-09

Published on: 2024-04-09

HGVS expressions

NM_001270448.2:c.1599+1G>A

NC_000017.11:g.7224885G>A

CM000679.2:g.7224885G>A

NC_000017.10:g.7128204G>A

CM000679.1:g.7128204G>A

NC_000017.9:g.7068928G>A

NG_007975.1:g.10052G>A

NG_008391.2:g.166C>T

NG_033038.1:g.14660C>T

ENST00000356839.10:c.1827+1G>A

ENST00000322910.9:c.*1782+1G>A

ENST00000350303.9:c.1761+1G>A

ENST00000356839.9:c.1827+1G>A

ENST00000542255.6:c.706+1G>A

ENST00000543245.6:c.1896+1G>A

ENST00000578033.1:n.252+1G>A

ENST00000578319.5:n.408+1G>A

ENST00000578711.1:n.1381G>A

ENST00000578809.5:n.399+1G>A

ENST00000579425.5:n.943+1G>A

ENST00000579546.1:c.562+1G>A

ENST00000583848.5:c.193+1G>A

ENST00000583850.5:n.598+1G>A

ENST00000583858.5:c.758+1G>A

NM_000018.3:c.1827+1G>A

NM_001033859.2:c.1761+1G>A

NM_001270447.1:c.1896+1G>A

NM_001270448.1:c.1599+1G>A

NM_000018.4:c.1827+1G>A

NM_001033859.3:c.1761+1G>A

NM_001270447.2:c.1896+1G>A

Pathogenic

PP4 PM2_Supporting PVS1

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1827+1G>A (NM_000018.4) variant in ACADVL occurs within the canonical splice donor/acceptor site (+/- 1,2) of intron 19. It is predicted to cause skipping of biologically-relevant-exon 19/20, 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). At least one patient with this variant displayed a positive newborn screen followed by reduced very long chain acyl-CoA dehydrogenase (VLCAD) enzyme activity, which is highly specific for VLCAD deficiency (PP4_Moderate, PMID: 30194637). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as 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, PP4_Moderate (ACADVL VCEP specifications version 1; approved November 9, 2021).

PP4

At least one patient with this variant displayed a positive newborn screen followed by reduced very long chain acyl-CoA dehydrogenase (VLCAD) enzyme activity, which is highly specific for VLCAD deficiency (PP4_Moderate, PMID: 30194637).

PM2_Supporting

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

PVS1

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