ClinVar Genomic variation as it relates to human health
NM_000018.4(ACADVL):c.192del (p.Lys64fs)
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
-
NM_000018.4(ACADVL):c.192del (p.Lys64fs)
Variation ID: 553583 Accession: VCV000553583.12
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 17p13.1 17: 7220512 (GRCh38) [ NCBI UCSC ] 17: 7123831 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Aug 5, 2018 Feb 28, 2024 Sep 23, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000018.4:c.192del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000009.1:p.Lys64fs frameshift NM_001033859.3:c.139-87del intron variant NM_001270447.2:c.261del NP_001257376.1:p.Lys87fs frameshift NM_001270448.2:c.-37del 5 prime UTR NC_000017.11:g.7220517del NC_000017.10:g.7123836del NG_007975.1:g.5684del NG_008391.2:g.4539del - Protein change
- K87fs, K64fs
- Other names
- NM_000018.4(ACADVL):c.192del
- p.Lys64fs
- Canonical SPDI
- NC_000017.11:7220511:AAAAAA:AAAAA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
ACADVL | - | - |
GRCh38 GRCh37 |
1703 | 1910 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Likely pathogenic (5) |
reviewed by expert panel
|
Sep 23, 2022 | RCV000669061.11 |
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
Help
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
Help
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
Help
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Sep 23, 2022)
|
reviewed by expert panel
Method: curation
|
Very long chain acyl-CoA dehydrogenase deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen ACADVL Variant Curation Expert Panel, ClinGen
Accession: SCV002576743.2
First in ClinVar: Oct 08, 2022 Last updated: Apr 23, 2023 |
Comment:
The c.192del (p.Lys64fs) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 3/20 leading to nonsense mediated … (more)
The c.192del (p.Lys64fs) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 3/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). The highest population minor allele frequency in gnomAD is 0.0001603 in the African population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). At least one patient with positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency has been reported with this variant (PMID: 26385305). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting. (less)
|
|
Likely pathogenic
(Aug 30, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000793762.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
|
|
Pathogenic
(Nov 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
|
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV001364951.2
First in ClinVar: Jul 16, 2020 Last updated: Jul 16, 2020 |
Comment:
The NM_000018.3:c.192delA (NP_000009.1:p.Lys64AsnfsTer53) [GRCH38: NC_000017.11:g.7220517delA] 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.192delA (NP_000009.1:p.Lys64AsnfsTer53) [GRCH38: NC_000017.11:g.7220517delA] 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)
|
|
Pathogenic
(Jan 06, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001578416.4
First in ClinVar: May 10, 2021 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Lys64Asnfs*53) in the ACADVL gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Lys64Asnfs*53) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). This variant is present in population databases (rs771055189, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with a positive newborn screening result for ACADVL-related disease (PMID: 26385305). ClinVar contains an entry for this variant (Variation ID: 553583). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Likely pathogenic
(Sep 03, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Very long chain acyl-CoA dehydrogenase deficiency
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004212637.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
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 |
---|---|---|---|---|
Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States. | Miller MJ | Molecular genetics and metabolism | 2015 | PMID: 26385305 |
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/16e07036-bca8-4df0-b774-3f934bb31e80 | - | - | - | - |
Text-mined citations for rs771055189 ...
HelpRecord last updated Feb 28, 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.