ClinVar Genomic variation as it relates to human health
NM_000235.4(LIPA):c.398del (p.Leu132_Ser133insTer)
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_000235.4(LIPA):c.398del (p.Leu132_Ser133insTer)
Variation ID: 289986 Accession: VCV000289986.19
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 10q23.31 10: 89228230 (GRCh38) [ NCBI UCSC ] 10: 90987987 (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 15, 2018 Feb 14, 2024 Nov 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000235.4:c.398del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000226.2:p.Leu132_Ser133insTer nonsense NM_000235.4:c.398delC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000235.3:c.398del NM_001127605.3:c.398del NP_001121077.1:p.Leu132_Ser133insTer nonsense NM_001288979.2:c.50del NP_001275908.1:p.Leu16_Ser17insTer nonsense NC_000010.11:g.89228230del NC_000010.10:g.90987987del NG_008194.1:g.28674del - Protein change
- Other names
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- Canonical SPDI
- NC_000010.11:89228229:G:
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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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD) 0.00008
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 | ||
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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
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. |
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LIPA | - | - |
GRCh38 GRCh37 |
641 | 672 |
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. |
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Pathogenic (1) |
criteria provided, single submitter
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Jan 9, 2018 | RCV000368412.6 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Feb 2, 2022 | RCV000801965.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 13, 2023 | RCV001376636.5 |
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. |
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Pathogenic
(Jan 09, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000344457.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Apr 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cholesteryl ester storage disease
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Centre for Inherited Metabolic Diseases, Karolinska University Hospital
Accession: SCV001554463.1
First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Family history: no
Secondary finding: no
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Pathogenic
(Nov 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cholesteryl ester storage disease
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV002060124.2
First in ClinVar: Jan 15, 2022 Last updated: Dec 24, 2022 |
Comment:
NM_000235.2(LIPA):c.398delC(S133*) is a nonsense variant classified as pathogenic in the context of lysosomal acid lipase deficiency. S133* has been observed in cases with relevant disease … (more)
NM_000235.2(LIPA):c.398delC(S133*) is a nonsense variant classified as pathogenic in the context of lysosomal acid lipase deficiency. S133* has been observed in cases with relevant disease (PMID: 11441129). Functional assessments of this variant are available in the literature (PMID: 11441129). S133* has been observed in population frequency databases (gnomAD: NFE 0.004%). In summary, NM_000235.2(LIPA):c.398delC(S133*) is a nonsense variant in a gene where loss of function is a known mechanism of disease, is predicted to disrupt protein function, and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cholesteryl ester storage disease
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002813880.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Nov 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Wolman disease
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000941771.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser133*) in the LIPA gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ser133*) in the LIPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LIPA are known to be pathogenic (PMID: 23485521). This variant is present in population databases (rs756016704, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with Wolman disease (PMID: 24832708, 28220406). ClinVar contains an entry for this variant (Variation ID: 289986). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Lysosomal acid lipase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001453548.1
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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Lysosomal Acid Lipase Deficiency in 23 Spanish Patients: High Frequency of the Novel c.966+2T>G Mutation in Wolman Disease. | Ruiz-Andrés C | JIMD reports | 2017 | PMID: 28220406 |
Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing. | Vega AI | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26913919 |
Infant case of lysosomal acid lipase deficiency: Wolman's disease. | Sadhukhan M | BMJ case reports | 2014 | PMID: 24832708 |
Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. | Bernstein DL | Journal of hepatology | 2013 | PMID: 23485521 |
Characterization of lysosomal acid lipase mutations in the signal peptide and mature polypeptide region causing Wolman disease. | Zschenker O | Journal of lipid research | 2001 | PMID: 11441129 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LIPA | - | - | - | - |
Text-mined citations for rs756016704 ...
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.