Variant: NM_000018.4(ACADVL):c.477+17G>A

CA8337710

386274 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: bd19d490-3ac5-4c17-96b0-a2ac723f4f2d

Approved on: 2023-04-11

Published on: 2023-04-11

HGVS expressions

NM_000018.4:c.477+17G>A
NM_000018.4(ACADVL):c.477+17G>A
NC_000017.11:g.7221075G>A
CM000679.2:g.7221075G>A
NC_000017.10:g.7124394G>A
CM000679.1:g.7124394G>A
NC_000017.9:g.7065118G>A
NG_007975.1:g.6242G>A
NG_008391.2:g.3976C>T
ENST00000356839.10:c.477+17G>A
ENST00000322910.9:c.*432+17G>A
ENST00000350303.9:c.411+17G>A
ENST00000356839.9:c.477+17G>A
ENST00000543245.6:c.546+17G>A
ENST00000577191.5:n.554+17G>A
ENST00000577433.5:n.685+17G>A
ENST00000577857.5:n.293+245G>A
ENST00000579286.5:n.658+17G>A
ENST00000579886.2:c.315+17G>A
ENST00000580365.1:n.208+17G>A
ENST00000581378.5:n.176+17G>A
ENST00000581562.5:n.524+17G>A
ENST00000582056.5:n.677G>A
ENST00000582166.1:n.458+17G>A
ENST00000583312.5:c.477+17G>A
NM_000018.3:c.477+17G>A
NM_001033859.2:c.411+17G>A
NM_001270447.1:c.546+17G>A
NM_001270448.1:c.249+17G>A
NM_001033859.3:c.411+17G>A
NM_001270447.2:c.546+17G>A
NM_001270448.2:c.249+17G>A

Uncertain Significance

• Met criteria codes: BP4 PM2_Supporting

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The c.477+17G>A variant in ACADVL is an intronic variant which occurs in intron 6. The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006 in the African population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0 for donor loss suggesting that the variant has no impact on splicing (BP4). In summary, this variant meets the criteria to be 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, BP4 (VCEP specifications v2.0, approved on 09/16/2021). This variant was originally curated March 8, 2022 and the recurated classification was approved by the expert panel on April 11, 2023.

Met criteria codes

• BP4: SpliceAI and MaxEntScan both predict no impact on splicing
• PM2_Supporting: gnomAD frequency is 0.00006238 in the African population with no homozygotes