NM_000018.4(ACADVL):c.1332+2T>C AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 9, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003846478.2

Allele description [Variation Report for NM_000018.4(ACADVL):c.1332+2T>C]

NM_000018.4(ACADVL):c.1332+2T>C

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000018.4(ACADVL):c.1332+2T>C

HGVS:

NC_000017.11:g.7223877T>C
NG_007975.1:g.9044T>C
NG_008391.2:g.1174A>G
NG_008391.3:g.1173A>G
NG_033038.1:g.15668A>G
NM_000018.4:c.1332+2T>CMANE SELECT
NM_001033859.3:c.1266+2T>C
NM_001270447.2:c.1401+2T>C
NM_001270448.2:c.1104+2T>C
NC_000017.10:g.7127196T>C

Molecular consequence:

NM_000018.4:c.1332+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001033859.3:c.1266+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001270447.2:c.1401+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001270448.2:c.1104+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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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LOC104935378 [Larimichthys crocea]
LOC104935378 [Larimichthys crocea]
Gene ID:104935378

Gene
ACER3 [Mesitornis unicolor]
ACER3 [Mesitornis unicolor]
Gene ID:104543825

Gene
CHPF [Charadrius vociferus]
CHPF [Charadrius vociferus]
Gene ID:104285702

Gene
AGPAT4 [Mesitornis unicolor]
AGPAT4 [Mesitornis unicolor]
Gene ID:104540799

Gene
TPST2 [Parus major]
TPST2 [Parus major]
Gene ID:107211790

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004694978	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 9, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 30194637, 16199547, 9973285, 11590124, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004694978

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 9, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).

Hesse J, Braun C, Behringer S, Matysiak U, Spiekerkoetter U, Tucci S.

J Inherit Metab Dis. 2018 Nov;41(6):1169-1178. doi: 10.1007/s10545-018-0245-5. Epub 2018 Sep 7.

PubMed [citation]

PMID:: 30194637

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004694978.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 30194637). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 13 of the ACADVL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124).

#	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: Sep 29, 2024

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