Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000018.4(ACADVL):c.1269G>A (p.Ser423=)

CA8338048

569548 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 142a9111-4aa0-4adc-bbfc-c69c7faa7696
Approved on: 2024-09-10
Published on: 2024-12-18

HGVS expressions

NM_000018.4:c.1269G>A
NM_000018.4(ACADVL):c.1269G>A (p.Ser423=)
NC_000017.11:g.7223730G>A
CM000679.2:g.7223730G>A
NC_000017.10:g.7127049G>A
CM000679.1:g.7127049G>A
NC_000017.9:g.7067773G>A
NG_007975.1:g.8897G>A
NG_008391.2:g.1321C>T
NG_033038.1:g.15815C>T
ENST00000356839.10:c.1269G>A
ENST00000322910.9:c.*1224G>A
ENST00000350303.9:c.1203G>A
ENST00000356839.9:c.1269G>A
ENST00000542255.6:c.127G>A
ENST00000543245.6:c.1338G>A
ENST00000578579.2:n.440G>A
ENST00000578711.1:n.226G>A
ENST00000578824.5:n.685G>A
ENST00000579425.5:n.293G>A
ENST00000579546.1:c.106G>A
ENST00000583850.5:n.44G>A
ENST00000583858.5:c.298G>A
ENST00000585203.6:n.477G>A
NM_000018.3:c.1269G>A
NM_001033859.2:c.1203G>A
NM_001270447.1:c.1338G>A
NM_001270448.1:c.1041G>A
NM_001033859.3:c.1203G>A
NM_001270447.2:c.1338G>A
NM_001270448.2:c.1041G>A
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Uncertain Significance

Met criteria codes 4
PM2_Supporting PM3_Supporting PP4_Moderate PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.1269G>A (NM_000018.4) variant in ACADVL is a synonymous variant which occurs in the final nucleotide of exon 12, a position that is generally considered highly conserved. At least one patient with this variant displayed reduced very long chain acyl-CoA dehydrogenase (VLCAD) enzyme levels in lymphocytes, which is highly specific for VLCAD deficiency (PP4_moderate, PMID: 30194637). The highest population minor allele frequency in gnomAD v2.1.1 is 0.000046 (0.0046%) in European (non-Finnish) 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 0.79 for donor loss, predicting that the variant disrupts the donor splice site of intron 12 of ACADVL (PP3). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM2_supporting, PP3, PP4_moderate (ACADVL VCEP specifications version 1; approved November 9, 2021).
Met criteria codes
PM2_Supporting
The highest population minor allele frequency in gnomAD v2.1.1 is 0.000046 (0.0046%) in European (non-Finnish) population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).
PM3_Supporting
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4_Moderate
At least one patient with this variant displayed reduced very long chain acyl-CoA dehydrogenase (VLCAD) enzyme levels in lymphocytes, which is highly specific for VLCAD deficiency (PP4_moderate, PMID: 30194637).
PP3
The computational splicing predictor SpliceAI gives a score of 0.79 for donor loss, predicting that the variant disrupts the donor splice site of intron 12 of ACADVL (PP3).
Curation History
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