ClinVar Genomic variation as it relates to human health
NM_152618.3(BBS12):c.1063C>T (p.Arg355Ter)
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_152618.3(BBS12):c.1063C>T (p.Arg355Ter)
Variation ID: 1147 Accession: VCV000001147.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q27 4: 122742955 (GRCh38) [ NCBI UCSC ] 4: 123664110 (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 Oct 20, 2014 Jun 17, 2024 Mar 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152618.3:c.1063C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689831.2:p.Arg355Ter nonsense NM_001178007.2:c.1063C>T NP_001171478.1:p.Arg355Ter nonsense NC_000004.12:g.122742955C>T NC_000004.11:g.123664110C>T NG_021203.1:g.15254C>T - Protein change
- R355*
- Other names
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- Canonical SPDI
- NC_000004.12:122742954:C:T
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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.
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The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
- Links
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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BBS12 | - | - |
GRCh38 GRCh37 |
777 | 804 |
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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Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Mar 16, 2024 | RCV000001206.16 | |
Pathogenic (2) |
criteria provided, single submitter
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Sep 10, 2023 | RCV000538405.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2017 | RCV000626780.2 | |
Pathogenic (1) |
no assertion criteria provided
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May 10, 2023 | RCV003228891.1 |
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
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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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Pathogenic
(Feb 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: yes
Allele origin:
germline
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Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals
Accession: SCV001156389.1
First in ClinVar: Feb 17, 2020 Last updated: Feb 17, 2020 |
Number of individuals with the variant: 1
Clinical Features:
Retinal dystrophy (present) , Polydactyly (present) , Intellectual disability (present) , Obesity (present) , Delayed speech and language development (present) , Nyctalopia (present) , Severe … (more)
Retinal dystrophy (present) , Polydactyly (present) , Intellectual disability (present) , Obesity (present) , Delayed speech and language development (present) , Nyctalopia (present) , Severe Myopia (present) (less)
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Pathogenic
(Apr 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002814272.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Sep 08, 2017)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
maternal
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV000680151.1
First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018 |
Sex: female
Tissue: blood
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Pathogenic
(Jan 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Inability to walk
Abnormal cardiovascular system morphology Postaxial polydactyly Visual impairment
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000747483.1
First in ClinVar: May 12, 2018 Last updated: May 12, 2018 |
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Pathogenic
(Mar 20, 2019)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001370443.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5.
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Pathogenic
(Sep 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000636538.5
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg355*) in the BBS12 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg355*) in the BBS12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 356 amino acid(s) of the BBS12 protein. This variant is present in population databases (rs121918327, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 17160889, 23591405). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1147). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211673.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Jan 01, 2007)
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no assertion criteria provided
Method: literature only
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BARDET-BIEDL SYNDROME 12
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000021356.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 20, 2014 |
Comment on evidence:
In 2 consanguineous Gypsy families, not known to be related and partially settled in 2 different regions of France, with Bardet-Biedl syndrome (BBS12; 615989), Stoetzel … (more)
In 2 consanguineous Gypsy families, not known to be related and partially settled in 2 different regions of France, with Bardet-Biedl syndrome (BBS12; 615989), Stoetzel et al. (2007) identified homozygosity for the same homozygous nonsense mutation in the BBS12 gene, 1062C-T, that resulted in an arg355-to-stop (R355X) substitution in the gene product. (less)
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Pathogenic
(Nov 27, 2017)
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no assertion criteria provided
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132342.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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Pathogenic
(May 10, 2023)
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no assertion criteria provided
Method: research
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Bardet-Biedl syndrome 1
Affected status: yes
Allele origin:
biparental,
inherited,
unknown
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Advanced Center For Translational And Genetic Medicine, Ann & Robert H. Lurie Children's Hospital Of Chicago
Accession: SCV003926581.1
First in ClinVar: May 27, 2023 Last updated: May 27, 2023 |
Observation 1: Observation 2: Observation 3: Observation 4: Observation 5: Observation 6: Observation 7: Observation 8: |
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Pathogenic
(Sep 15, 2018)
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no assertion criteria provided
Method: provider interpretation
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Bardet-Biedl syndrome
Affected status: yes
Allele origin:
germline
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Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University
Study: French fetal BBS cohort
Accession: SCV000839573.1 First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Ethnicity/Population group: Gypsy
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Bardet-Biedl syndrome type 12
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001462013.1
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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Bardet-Biedl syndrome: Antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes. | Mary L | Clinical genetics | 2019 | PMID: 30614526 |
Panel-based next generation sequencing as a reliable and efficient technique to detect mutations in unselected patients with retinal dystrophies. | Glöckle N | European journal of human genetics : EJHG | 2014 | PMID: 23591405 |
Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome. | Stoetzel C | American journal of human genetics | 2007 | PMID: 17160889 |
Text-mined citations for rs121918327 ...
HelpRecord last updated Sep 29, 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.