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]

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

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA658798683

541714 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

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

Approved on: 2022-04-06

Published on: 2022-07-12

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"

PVS1 PM2_Supporting

PP4 PM3 BP7

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

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).

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).

PM2_Supporting

PM2_Supporting (met). This variant is absent from gnomAD 2.1.1 (PM2_Supporting).

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.

BP7

Criterion not met because variant is a deletion predicted to result in a frameshift and premature termination codon.

Curation History

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