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_001270448.2:c.649C>T

CA397723872

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 69a5895c-507c-4c27-bc1b-1a2afb99ec70

HGVS expressions

NM_001270448.2:c.649C>T

NC_000017.11:g.7222301C>T

CM000679.2:g.7222301C>T

NC_000017.10:g.7125620C>T

CM000679.1:g.7125620C>T

NC_000017.9:g.7066344C>T

NG_007975.1:g.7468C>T

NG_008391.2:g.2750G>A

ENST00000356839.10:c.877C>T

ENST00000322910.9:c.*832C>T

ENST00000350303.9:c.811C>T

ENST00000356839.9:c.877C>T

ENST00000543245.6:c.946C>T

ENST00000577191.5:n.1049C>T

ENST00000581378.5:c.595C>T

ENST00000582379.1:n.261C>T

NM_000018.3:c.877C>T

NM_001033859.2:c.811C>T

NM_001270447.1:c.946C>T

NM_001270448.1:c.649C>T

NM_000018.4:c.877C>T

NM_001033859.3:c.811C>T

NM_001270447.2:c.946C>T

Uncertain Significance

PM3_Supporting PM2_Supporting PP4_Moderate

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4(ACADVL): c.877C>T variant in ACADVL is a missense variant predicted to cause substitution of histamine by tyrosine at amino acid 293 (p.His293Tyr). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been co-detected with a p.Gly441Asp pathogenic variant in an individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency with unknown phase confirmation (PM3 point 0.5, PM3_Supporting, PMIDs: 25834949). This patient also displayed reduced enzyme levels (< 20 % of wildtype), which is highly specific for VLCAD deficiency (PP4_Moderate, PMID: 25834949). The computational predictor REVEL gives a score of 0.494, which is neither above nor below the thresholds predicting a damaging or benign impact on ACADVL function. Due to conflicting evidence, this variant is classified as a variant of uncertain significance 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: PM2_Supporting, PM3_Supporting, PP4_Moderate (ACADVL VCEP specifications version 1; approved November 9, 2021).

PM3_Supporting

This variant has been co-detected with a p.Gly441Asp pathogenic variant in an individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency with unknown phase confirmation (PM3 point 0.5, PM3_Supporting, PMIDs: 25834949).

PM2_Supporting

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

PP4_Moderate

This patient also displayed reduced enzyme levels (< 20 % of wildtype), which is highly specific for VLCAD deficiency (PP4_Moderate, PMID: 25834949).

Approved on: 2023-11-13

Published on: 2023-11-13

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