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_000018.4:c.1966T>A

CA397726273

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0a906e4f-b71a-403e-8791-eb24efee9601

Approved on: 2022-09-23

Published on: 2022-09-23

HGVS expressions

NM_000018.4:c.1966T>A

NC_000017.11:g.7225095T>A

CM000679.2:g.7225095T>A

NC_000017.10:g.7128414T>A

CM000679.1:g.7128414T>A

NC_000017.9:g.7069138T>A

NG_007975.1:g.10262T>A

NG_033038.1:g.14450A>T

ENST00000356839.10:c.1966T>A

ENST00000322910.9:c.*1921T>A

ENST00000350303.9:c.1900T>A

ENST00000356839.9:c.1966T>A

ENST00000542255.6:n.845T>A

ENST00000543245.6:c.2035T>A

ENST00000578033.1:n.391T>A

ENST00000578319.5:n.547T>A

ENST00000578711.1:n.1591T>A

ENST00000578809.5:n.538T>A

ENST00000579425.5:n.1082T>A

ENST00000583848.5:n.332T>A

ENST00000583850.5:n.737T>A

ENST00000583858.5:n.897T>A

NM_000018.3:c.1966T>A

NM_001033859.2:c.1900T>A

NM_001270447.1:c.2035T>A

NM_001270448.1:c.1738T>A

NM_001033859.3:c.1900T>A

NM_001270447.2:c.2035T>A

NM_001270448.2:c.1738T>A

Uncertain Significance

PM2_Supporting PM4

PP4 PP3 PM5

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1966T>A variant in ACADVL is a stop-loss predicted to result in a 32-aa peptide extension at the C-terminus (PM4). This variant has been identified in one individual as a heterozygote identified by abnormal newborn screening results suggestive of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (PMID: 30194637). This study also showed reduced VLCAD activity in patient lymphocytes, however, this assay does not meet the requirements for use by the ClinGen ACADVL Variant Curation Expert Panel. This variant is absent from gnomAD v2.1.1 (PM2_Supporting).In summary, this variant meets the criteria to be classified as uncertain 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: (PM4, PM2_Supporting)

PM2_Supporting

Not present in gnomAD

PM4

Additional 32-aa peptide at the C-terminus via stop-loss variant

PP4

Reported as a heterozygote with WT. Residual enzyme activity is ~33%, not meeting PP4_moderate.

PP3

Available computational evidence does not provide predictions for this variant.

PM5

c.1968A>C is at the same codon, but is not LP or P

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