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.1605+2T>A

CA397725472

932832 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4afef496-072c-4eb8-a20b-8c10399cbc8f

HGVS expressions

NM_000018.4:c.1605+2T>A

NM_000018.4(ACADVL):c.1605+2T>A

NC_000017.11:g.7224395T>A

CM000679.2:g.7224395T>A

NC_000017.10:g.7127714T>A

CM000679.1:g.7127714T>A

NC_000017.9:g.7068438T>A

NG_007975.1:g.9562T>A

NG_008391.2:g.656A>T

NG_033038.1:g.15150A>T

ENST00000356839.10:c.1605+2T>A

ENST00000322910.9:c.*1560+2T>A

ENST00000350303.9:c.1539+2T>A

ENST00000356839.9:c.1605+2T>A

ENST00000542255.6:n.463+2T>A

ENST00000543245.6:c.1674+2T>A

ENST00000578319.5:n.102T>A

ENST00000578711.1:n.891T>A

ENST00000578809.5:n.177+2T>A

ENST00000579391.1:n.213+2T>A

ENST00000579425.5:n.721+2T>A

ENST00000579546.1:n.344+2T>A

ENST00000579894.5:n.392+2T>A

ENST00000582450.1:n.113+2T>A

ENST00000583074.5:n.226+2T>A

ENST00000583850.5:n.380+2T>A

ENST00000583858.5:n.536+2T>A

ENST00000585203.6:n.796+2T>A

NM_000018.3:c.1605+2T>A

NM_001033859.2:c.1539+2T>A

NM_001270447.1:c.1674+2T>A

NM_001270448.1:c.1377+2T>A

NM_001033859.3:c.1539+2T>A

NM_001270447.2:c.1674+2T>A

NM_001270448.2:c.1377+2T>A

Likely Pathogenic

PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specification: ClinGen ACADVL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1605+2T>A (p.?) variant in ACADVL occurs within the canonical splice donor site (+2) of intron 16. It is predicted to cause skipping of biologically-relevant-exon 16/20, 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). To our knowledge, this variant has not been reported in the literature in any individuals with VLCADD. To our knowledge, functional assays have not been reported for this variant. This variant is absent from gnomAD 2.1.1 (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 (ClinGen ACADVL VCEP specifications version#1; 09-05-2022).

PVS1

PVS1 is met. The c.1605+2T>A (p.?) variant in ACADVL occurs within the canonical splice donor site (+2) of intron 16. It is predicted to cause skipping of biologically-relevant-exon 16/20, 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).

PM2_Supporting

PM2_Supporting is met. This variant is absent from gnomAD 2.1.1 (PM2_Supporting).

Approved on: 2022-09-05

Published on: 2023-06-29

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