NM_000018.4(ACADVL):c.1534_1535del (p.Arg512fs) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 29, 2023
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001200785.2

Allele description [Variation Report for NM_000018.4(ACADVL):c.1534_1535del (p.Arg512fs)]

NM_000018.4(ACADVL):c.1534_1535del (p.Arg512fs)

Gene:

ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000018.4(ACADVL):c.1534_1535del (p.Arg512fs)

Other names:

NM_000018.4(ACADVL):c.1534_1535del; p.Arg512fs

HGVS:

NC_000017.11:g.7224322_7224323del
NG_007975.1:g.9489_9490del
NG_008391.2:g.729_730del
NG_033038.1:g.15223_15224del
NM_000018.4:c.1534_1535delMANE SELECT
NM_001033859.3:c.1468_1469del
NM_001270447.2:c.1603_1604del
NM_001270448.2:c.1306_1307del
NP_000009.1:p.Arg512fs
NP_001029031.1:p.Arg490fs
NP_001257376.1:p.Arg535fs
NP_001257377.1:p.Arg436fs
NC_000017.10:g.7127641_7127642del
NM_000018.3:c.1534_1535delCG

Protein change:

R436fs

Links:

dbSNP: rs2071371983

NCBI 1000 Genomes Browser:

rs2071371983

Molecular consequence:

NM_000018.4:c.1534_1535del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001033859.3:c.1468_1469del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270447.2:c.1603_1604del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270448.2:c.1306_1307del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Very long chain acyl-CoA dehydrogenase deficiency (ACADVLD)
Synonyms:: VLCAD deficiency
Identifiers:: MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001364982	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 1, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003936870	ClinGen ACADVL Variant Curation Expert Panel, ClinGen	reviewed by expert panel (clingen acadvl acmg specifications v1)	Likely pathogenic (Jun 29, 2023)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001364982

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 1, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003936870

ClinGen ACADVL Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(clingen acadvl acmg specifications v1)

Likely pathogenic
(Jun 29, 2023)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001364982.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The NM_000018.3:c.1534_1535delCG (NP_000009.1:p.Arg512GlyfsTer49) [GRCH38: NC_000017.11:g.7224322_7224323del] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ClinGen ACADVL Variant Curation Expert Panel, ClinGen, SCV003936870.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The c.1534_1535del (p.Arg512GlyfsTer49) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 17/20 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 meets the criteria to be classified as LIKELY PATHOGENIC 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: PVS1, PM2_Supporting (ClinGen ACADVL VCEP specifications version#1.0; approved 12-29-22).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 16, 2023

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