ClinVar Genomic variation as it relates to human health
NM_001378454.1(ALMS1):c.6302C>A (p.Ser2101Ter)
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.6302C>A (p.Ser2101Ter)
Variation ID: 871762 Accession: VCV000871762.37
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p13.1 2: 73452829 (GRCh38) [ NCBI UCSC ] 2: 73679956 (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 May 12, 2020 Apr 15, 2024 Feb 5, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001378454.1:c.6302C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001365383.1:p.Ser2101Ter nonsense NM_015120.4:c.6305C>A NP_055935.4:p.Ser2102Ter nonsense NC_000002.12:g.73452829C>A NC_000002.11:g.73679956C>A NG_011690.1:g.72077C>A LRG_741:g.72077C>A LRG_741t1:c.6305C>A LRG_741p1:p.Ser2102Ter - Protein change
- S2101*, S2102*
- Other names
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- Canonical SPDI
- NC_000002.12:73452828:C: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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0.01478 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- 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 | ||
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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
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 |
5947 | 6254 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Jun 25, 2020 | RCV001091888.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 8, 2020 | RCV001266523.3 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Feb 5, 2024 | RCV001230120.13 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 11, 2021 | RCV002365792.2 |
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
(Jun 25, 2020)
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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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GeneDx
Accession: SCV001770596.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 17594715, 31106028, 29302074, 30488743, 30064963) (less)
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Pathogenic
(Apr 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Alstrom syndrome
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002499424.1
First in ClinVar: Apr 16, 2022 Last updated: Apr 16, 2022 |
Comment:
The c.6305C>A;p.(Ser2102*) variant creates a premature translational stop signal in the ALMS1 gene. It is expected to result in an absent or disrupted protein product … (more)
The c.6305C>A;p.(Ser2102*) variant creates a premature translational stop signal in the ALMS1 gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 871762; PMID: 30488743; 30064963; 17594715) - PS4. The variant is present at low allele frequencies population databases (rs28730854 – gnomAD 0.0004602%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. The p.(Ser2102*) was detected in trans with a pathogenic variant (PMID: 30488743; 30064963; 17594715) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Brazil
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Pathogenic
(Jan 11, 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: SCV002660575.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.S2102* pathogenic mutation (also known as c.6305C>A), located in coding exon 8 of the ALMS1 gene, results from a C to A substitution at … (more)
The p.S2102* pathogenic mutation (also known as c.6305C>A), located in coding exon 8 of the ALMS1 gene, results from a C to A substitution at nucleotide position 6305. This changes the amino acid from a serine to a stop codon within coding exon 8. This mutation has been reported in the compound heterozygous state with other alterations which are expected to be pathogenic or likely pathogenic in several individuals with Alstrom syndrome or related features (Marshall JD et al. Hum Mutat, 2007 Nov;28:1114-23; Citton V et al. J Neuroradiol, 2016 Jun;43:195-9; Han JC et al. J Clin Endocrinol Metab, 2018 07;103:2707-2719; Hu H et al. Mol Psychiatry, 2019 07;24:1027-1039; Wang P et al. Transl Vis Sci Technol, 2019 Mar;8:21). 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)
Number of individuals with the variant: 1
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Pathogenic
(Oct 26, 2021)
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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: SCV002799605.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 08, 2020)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV001444698.2
First in ClinVar: Nov 21, 2020 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Photophobia (present) , Autistic disorder of childhood onset (present) , Global developmental delay (present) , Obesity (present) , Nystagmus (present) , Cone/cone-rod dystrophy (present) , … (more)
Photophobia (present) , Autistic disorder of childhood onset (present) , Global developmental delay (present) , Obesity (present) , Nystagmus (present) , Cone/cone-rod dystrophy (present) , Hypermetropia (present) (less)
Sex: male
Ethnicity/Population group: African American/Caucasian
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Pathogenic
(Jun 01, 2021)
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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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Baylor Genetics
Accession: SCV003835053.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Dec 25, 2023)
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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: SCV001402590.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser2102*) 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.Ser2102*) 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 (rs28730854, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Alstrom syndrome (PMID: 17594715, 30488743). ClinVar contains an entry for this variant (Variation ID: 871762). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248155.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Feb 05, 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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004813075.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
Variant summary: ALMS1 c.6299C>A (p.Ser2100X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is … (more)
Variant summary: ALMS1 c.6299C>A (p.Ser2100X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 2e-05 in 247674 control chromosomes. c.6299C>A has been reported in the literature in at-least one individual affected with Alstrom Syndrome (example, Bahena_2021). These data indicate that the variant is very likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34148116). ClinVar contains an entry for this variant (Variation ID: 871762). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Aug 19, 2021)
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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: SCV002082825.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment. | Bahena P | Human genetics | 2022 | PMID: 34148116 |
An Ophthalmic Targeted Exome Sequencing Panel as a Powerful Tool to Identify Causative Mutations in Patients Suspected of Hereditary Eye Diseases. | Wang P | Translational vision science & technology | 2019 | PMID: 31106028 |
Non-syndromic retinal dystrophy associated with homozygous mutations in the ALMS1 gene. | Aldrees A | Ophthalmic genetics | 2019 | PMID: 30488743 |
Genetics of intellectual disability in consanguineous families. | Hu H | Molecular psychiatry | 2019 | PMID: 29302074 |
Alström syndrome: Renal findings in correlation with obesity, insulin resistance, dyslipidemia and cardiomyopathy in 38 patients prospectively evaluated at the NIH clinical center. | Waldman M | Molecular genetics and metabolism | 2018 | PMID: 30064963 |
Comprehensive Endocrine-Metabolic Evaluation of Patients With Alström Syndrome Compared With BMI-Matched Controls. | Han JC | The Journal of clinical endocrinology and metabolism | 2018 | PMID: 29718281 |
Pituitary morphovolumetric changes in Alström syndrome. | Citton V | Journal of neuroradiology = Journal de neuroradiologie | 2016 | PMID: 26704672 |
Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. | Marshall JD | Human mutation | 2007 | PMID: 17594715 |
Text-mined citations for rs28730854 ...
HelpRecord last updated Apr 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.