Variant: NM_000018.4(ACADVL):c.103_112del (p.Pro35fs)

CA658798683

541714 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 3ae146a3-48f2-4971-aee0-7611b3bd4b38

HGVS expressions

NM_000018.4:c.103_112del
NM_000018.4(ACADVL):c.103_112del (p.Pro35fs)
NC_000017.11:g.7220162_7220171del
CM000679.2:g.7220162_7220171del
NC_000017.10:g.7123481_7123490del
CM000679.1:g.7123481_7123490del
NC_000017.9:g.7064205_7064214del
NG_007975.1:g.5329_5338del
NG_008391.2:g.4887_4896del
ENST00000356839.10:c.103_112del
ENST00000322910.9:c.*58_*67del
ENST00000350303.9:c.103_112del
ENST00000356839.9:c.103_112del
ENST00000543245.6:c.172_181del
ENST00000577191.5:n.180_189del
ENST00000577857.5:n.193_202del
ENST00000578269.5:n.210_219del
ENST00000578421.1:n.237_246del
ENST00000579286.5:n.210_219del
ENST00000579886.2:c.103_112del
ENST00000580263.5:n.193_202del
ENST00000581562.5:n.150_159del
ENST00000582056.5:n.193_202del
ENST00000582356.5:n.228_237del
ENST00000583312.5:c.103_112del
ENST00000584103.5:c.103_112del
NM_000018.3:c.103_112del
NM_001033859.2:c.103_112del
NM_001270447.1:c.172_181del
NM_001270448.1:c.-126_-117del
NM_001033859.3:c.103_112del
NM_001270447.2:c.172_181del
NM_001270448.2:c.-126_-117del

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

• Met criteria codes: PM2_Supporting PVS1

• Not Met criteria codes: BP7 PP4 PM3

Expert Panel

ACADVL VCEP

Criteria Specification Information

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

Evidence submitted by expert panel

ACADVL VCEP

The c.103_112del (p.(Pro35Glyfs*23)) (NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 2/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs: 9973285, 11590124). This variant is absent from gnomAD 2.1.1 (PM2_Supporting). To our knowledge, functional assays have not been reported for this variant. To our knowledge, this variant has not been reported in the literature in any individuals with VLCADD. In summary, this variant has been classified as likely pathogenic for autosomal recessive very long chain acyl-CoA dehydrogenase deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Curation Expert Panel: PVS1, PM2_Supporting (ACADVL VCEP specifications v2.0; Approved on 11/10/2021).

Met criteria codes

• PM2_Supporting: PM2_Supporting (met). This variant is absent from gnomAD 2.1.1 (PM2_Supporting).
• PVS1: PVS1 met. The c.103_112del (p.(Pro35Glyfs*23)) (NM_000018.4) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 2/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs: 9973285, 11590124).

Not Met criteria codes

• BP7: Criterion not met because variant is a deletion predicted to result in a frameshift and premature termination codon.
• PP4: To our knowledge, this variant has not been reported in the literature.
• PM3: To our knowledge, this variant has not been reported in the literature.

Approved on: 2022-04-06

Published on: 2022-07-12