ClinVar Genomic variation as it relates to human health
NM_001378454.1(ALMS1):c.2819T>A (p.Leu940Ter)
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_001378454.1(ALMS1):c.2819T>A (p.Leu940Ter)
Variation ID: 224801 Accession: VCV000224801.41
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p13.1 2: 73449346 (GRCh38) [ NCBI UCSC ] 2: 73676473 (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 Mar 31, 2016 May 1, 2024 Jan 4, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001378454.1:c.2819T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001365383.1:p.Leu940Ter nonsense NM_015120.4:c.2822T>A NP_055935.4:p.Leu941Ter nonsense NC_000002.12:g.73449346T>A NC_000002.11:g.73676473T>A NG_011690.1:g.68594T>A LRG_741:g.68594T>A LRG_741t1:c.2822T>A LRG_741p1:p.Leu941Ter - Protein change
- L941*, L940*
- Other names
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- Canonical SPDI
- NC_000002.12:73449345:T:A
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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.
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
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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ALMS1 | - | - |
GRCh38 GRCh38 GRCh37 |
6007 | 6318 |
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 (5) |
criteria provided, multiple submitters, no conflicts
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Jan 4, 2024 | RCV000210366.16 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 9, 2018 | RCV001818509.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 6, 2021 | RCV002433919.2 |
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
(Dec 01, 2015)
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criteria provided, single submitter
Method: research
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Alstrom syndrome
Affected status: yes
Allele origin:
unknown
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Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS
Accession: SCV000259178.4
First in ClinVar: Mar 31, 2016 Last updated: Mar 31, 2016
Comment:
Nonsense mutation
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Clinical Features:
Global developmental delay (present) , Truncal obesity (present) , Blindness (present)
Indication for testing: Developmental delay, truncal obesity, vision problems
Age: 0-9 years
Sex: male
Geographic origin: India
Method: Whole Exome Sequencing; Sanger sequencing; cDNA analysis
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Pathogenic
(Dec 09, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002069210.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Pathogenic
(Aug 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Alstrom syndrome
Affected status: yes
Allele origin:
inherited
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Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University
Accession: SCV002559828.2
First in ClinVar: Feb 13, 2023 Last updated: Aug 13, 2023 |
Number of individuals with the variant: 5
Family history: yes
Secondary finding: no
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Pathogenic
(Jan 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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Alstrom syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000756143.7
First in ClinVar: Mar 31, 2016 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Leu941*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Leu941*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is present in population databases (rs539612316, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with Alstrom syndrome (PMID: 26111748, 27665122). ClinVar contains an entry for this variant (Variation ID: 224801). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002746667.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.L941* pathogenic mutation (also known as c.2822T>A), located in coding exon 8 of the ALMS1 gene, results from a T to A substitution at … (more)
The p.L941* pathogenic mutation (also known as c.2822T>A), located in coding exon 8 of the ALMS1 gene, results from a T to A substitution at nucleotide position 2822. This changes the amino acid from a leucine to a stop codon within coding exon 8. This mutation (also referred to as c.2816T>A, p.L939*) has been detected in the homozygous state and in the compound heterozygous state with ALMS1 nonsense and frameshift alleles in individuals with Alstrom syndrome (Marshall JD et al. Hum Mutat, 2015 Jul;36:660-8; Das Bhowmik A et al. Obes Res Clin Pract , 2017 Sep;11:241-246; Baig S et al. Orphanet J Rare Dis, 2020 06;15:139). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Apr 06, 2022)
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criteria provided, single submitter
Method: clinical testing
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Alstrom syndrome
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002808687.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Alstrom syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001458918.1
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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Prospective cardiovascular magnetic resonance imaging in adults with Alström syndrome: silent progression of diffuse interstitial fibrosis. | Baig S | Orphanet journal of rare diseases | 2020 | PMID: 32503575 |
Whole exome sequencing identifies a homozygous nonsense variation in ALMS1 gene in a patient with syndromic obesity. | Das Bhowmik A | Obesity research & clinical practice | 2017 | PMID: 27665122 |
Histopathology of the human inner ear in Alström's syndrome. | Nadol JB Jr | Audiology & neuro-otology | 2015 | PMID: 26111748 |
Alström Syndrome: Mutation Spectrum of ALMS1. | Marshall JD | Human mutation | 2015 | PMID: 25846608 |
Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. | Marshall JD | Human mutation | 2007 | PMID: 17594715 |
- | - | - | - | DOI: doi:10.1155/2023/2564200 |
Text-mined citations for rs539612316 ...
HelpRecord last updated May 08, 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.