ClinVar Genomic variation as it relates to human health
NM_152618.3(BBS12):c.2023C>T (p.Arg675Ter)
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.2023C>T (p.Arg675Ter)
Variation ID: 347505 Accession: VCV000347505.58
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q27 4: 122743915 (GRCh38) [ NCBI UCSC ] 4: 123665070 (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 6, 2016 May 12, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152618.3:c.2023C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689831.2:p.Arg675Ter nonsense NM_001178007.2:c.2023C>T NP_001171478.1:p.Arg675Ter nonsense NC_000004.12:g.122743915C>T NC_000004.11:g.123665070C>T NG_021203.1:g.16214C>T - Protein change
- R675*
- Other names
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- Canonical SPDI
- NC_000004.12:122743914: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.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
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 |
726 | 752 |
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 (2) |
criteria provided, single submitter
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Jan 31, 2024 | RCV000302878.8 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Oct 4, 2023 | RCV000670073.12 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jul 10, 2021 | RCV001091376.20 | |
BBS12-related disorder
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Pathogenic (1) |
criteria provided, single submitter
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Jun 12, 2023 | RCV003418071.4 |
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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Likely pathogenic
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000447429.3
First in ClinVar: Dec 06, 2016 Last updated: May 27, 2019 |
Comment:
The BBS12 c.2023C>T (p.Arg675Ter) stop-gained variant has been reported in two studies in a total of three individuals, either with Bardet-Biedl syndrome (BBS) or suspected … (more)
The BBS12 c.2023C>T (p.Arg675Ter) stop-gained variant has been reported in two studies in a total of three individuals, either with Bardet-Biedl syndrome (BBS) or suspected to have BBS, in a compound heterozygous state (Dulfer et al. 2010; Chen et al. 2011). Of these individuals, two were siblings who also had a heterozygous frameshift variant in the BBS10 gene. In this family, the father was heterozygous for the BBS12 p.Arg675Ter variant and the mother was heterozygous for the other variants. The other individual who had the p.Arg675Ter variant in a compound heterozygous state also had a heterozygous missense variant in the BBS1 gene. The p.Arg675Ter variant was absent from 288 controls but is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium, however this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Based on the evidence and due to potential impact of stop-gained variants, the p.Arg675Ter variant is classified as likely pathogenic for Bardet-Biedl syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Oct 31, 2018)
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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: SCV000894332.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Likely pathogenic
(Jul 10, 2021)
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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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Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755374.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Indication for testing: Bardet-Biedl syndrome
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Pathogenic
(Jan 31, 2024)
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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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Invitae
Accession: SCV000759859.5
First in ClinVar: Dec 06, 2016 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg675*) 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.Arg675*) in the BBS12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acid(s) of the BBS12 protein. This variant is present in population databases (rs752202089, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 20827784, 21642631). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 347505). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 01, 2016)
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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: SCV001247391.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Likely pathogenic
(-)
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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:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004048011.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The stop gain variant c.2023C>T (p.Arg675Ter) in the BBS12 gene has been reported previously in a compound heterozygous state in patients affected with Bardet–Biedl Syndrome. … (more)
The stop gain variant c.2023C>T (p.Arg675Ter) in the BBS12 gene has been reported previously in a compound heterozygous state in patients affected with Bardet–Biedl Syndrome. Two of the patients also had a heterozygous frameshift variant in the BBS10 gene along with the BBS12 variants (Dulfer E. et al., 2010). This variant is reported with the allele frequency (0.0008%) in the gnomAD Exomes and novel in 1000 genome database. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic (less)
Clinical Features:
Postaxial polydactyly (present) , Obesity (present)
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Pathogenic
(Jun 12, 2023)
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criteria provided, single submitter
Method: clinical testing
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BBS12-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004114122.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The BBS12 c.2023C>T variant is predicted to result in premature protein termination (p.Arg675*). This variant has been reported to be causative for Bardet-Biedl syndrome (Dulfer. … (more)
The BBS12 c.2023C>T variant is predicted to result in premature protein termination (p.Arg675*). This variant has been reported to be causative for Bardet-Biedl syndrome (Dulfer. 2010. PubMed ID: 20827784; Mary et al. 2019. PubMed ID: 30614526). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-123665070-C-T). Nonsense variants in BBS12 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Oct 04, 2023)
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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: SCV004211662.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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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: SCV000839577.1 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Age: 20-29 weeks gestation
Ethnicity/Population group: Middle East
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Pathogenic
(Oct 18, 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: SCV000794888.2
First in ClinVar: Aug 05, 2018 Last updated: May 27, 2019 |
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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: SCV001462026.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001952171.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001971445.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 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 |
Molecular analysis of Bardet-Biedl syndrome families: report of 21 novel mutations in 10 genes. | Chen J | Investigative ophthalmology & visual science | 2011 | PMID: 21642631 |
Two sibs with Bardet-Biedl syndrome due to mutations in BBS12: no clues for modulation by a third mutation in BBS10. | Dulfer E | American journal of medical genetics. Part A | 2010 | PMID: 20827784 |
Text-mined citations for rs752202089 ...
HelpRecord last updated May 27, 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.