ClinVar Genomic variation as it relates to human health
NM_000018.4(ACADVL):c.63-2A>C
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000018.4(ACADVL):c.63-2A>C
Variation ID: 474900 Accession: VCV000474900.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 7220120 (GRCh38) [ NCBI UCSC ] 17: 7123439 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 26, 2017 Feb 20, 2024 Mar 8, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000018.4:c.63-2A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001033859.3:c.63-2A>C splice acceptor NM_001270447.2:c.132-2A>C splice acceptor NM_001270448.2:c.-168A>C 5 prime UTR NC_000017.11:g.7220120A>C NC_000017.10:g.7123439A>C NG_007975.1:g.5287A>C NG_008391.2:g.4931T>G NG_008391.3:g.4930T>G - Protein change
- Other names
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- Canonical SPDI
- NC_000017.11:7220119:A:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ACADVL | - | - |
GRCh38 GRCh37 |
1704 | 1909 | |
LOC130060113 | - | - | - | GRCh38 | - | 90 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely pathogenic (4) |
reviewed by expert panel
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Mar 8, 2022 | RCV000531909.11 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Mar 08, 2022)
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reviewed by expert panel
Method: curation
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Very long chain acyl-CoA dehydrogenase deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen ACADVL Variant Curation Expert Panel, ClinGen
Accession: SCV002576787.2
First in ClinVar: Oct 08, 2022 Last updated: Apr 23, 2023 |
Comment:
The c.63-2A>C variant in ACADVL occurs within the canonical splice acceptor site (+/- 1,2) of intron 1. It is predicted to cause skipping of biologically-relevant-exon … (more)
The c.63-2A>C variant in ACADVL occurs within the canonical splice acceptor site (+/- 1,2) of intron 1. It is predicted to cause skipping of biologically-relevant-exon 2/20, resulting in a frameshift 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 v2.1.1 (PM2_Supporting). This variant has been reported in an abnormal newborn screen without clinical confirmation or a second pathogenic ACADVL variant identified (PMID 26385305, 27209629). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting (VCEP specifications v2.0, approved on 09/16/2021). (less)
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Pathogenic
(Nov 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV001364945.2
First in ClinVar: Jul 16, 2020 Last updated: Jul 16, 2020 |
Comment:
The NM_000018.3:c.63-2A>C (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7220120A>C] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. … (more)
The NM_000018.3:c.63-2A>C (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7220120A>C] 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 (less)
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Likely pathogenic
(Jan 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000654959.3
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 1 of the ACADVL gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 1 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 27209629). ClinVar contains an entry for this variant (Variation ID: 474900). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Likely pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001455118.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database. | Pena LD | Molecular genetics and metabolism | 2016 | PMID: 27209629 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. | Cox KB | Human molecular genetics | 2001 | PMID: 11590124 |
Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency. | Andresen BS | American journal of human genetics | 1999 | PMID: 9973285 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/5c62664a-7354-47c7-87a8-0b26feb8a5b9 | - | - | - | - |
Text-mined citations for rs1555527513 ...
HelpRecord last updated Feb 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.