ClinVar Genomic variation as it relates to human health
NM_152618.3(BBS12):c.1893_1894del (p.Pro632fs)
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.1893_1894del (p.Pro632fs)
Variation ID: 866623 Accession: VCV000866623.39
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 4q27 4: 122743782-122743783 (GRCh38) [ NCBI UCSC ] 4: 123664937-123664938 (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 Apr 18, 2020 Mar 16, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152618.3:c.1890_1891del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_152618.3:c.1893_1894del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689831.2:p.Pro632fs frameshift NM_001178007.2:c.1893_1894del NP_001171478.1:p.Pro632fs frameshift NM_152618.2:c.1893_1894delTC NC_000004.12:g.122743783TC[1] NC_000004.11:g.123664938TC[1] NG_021203.1:g.16082TC[1] - Protein change
- P632fs
- Other names
- NM_152618.3(BBS12):c.1893_1894del
- p.Pro632fs
- Canonical SPDI
- NC_000004.12:122743781:CTCTC:CTC
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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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- 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
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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
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
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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 (1) |
criteria provided, single submitter
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Jun 20, 2019 | RCV001074774.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 6, 2023 | RCV001238322.4 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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May 2, 2023 | RCV001281169.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV003918665.1 |
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
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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 20, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001240369.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Pathogenic
(Feb 01, 2020)
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criteria provided, single submitter
Method: research
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Bardet-Biedl syndrome 12
Affected status: yes
Allele origin:
paternal
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Molecular Biology Laboratory, Fundació Puigvert
Study: KidneyPanel_2020
Accession: SCV001424981.1 First in ClinVar: Jan 17, 2021 Last updated: Jan 17, 2021 |
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Pathogenic
(Aug 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: yes
Allele origin:
inherited
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Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University
Accession: SCV002559830.2
First in ClinVar: Feb 13, 2023 Last updated: Aug 13, 2023 |
Number of individuals with the variant: 8
Secondary finding: no
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Likely pathogenic
(Apr 20, 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: SCV002813959.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(May 02, 2023)
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criteria provided, single submitter
Method: curation
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Bardet-Biedl syndrome 12
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV003922204.1
First in ClinVar: May 06, 2023 Last updated: May 06, 2023 |
Comment:
The heterozygous p.Pro632PhefsTer7 variant in BBS12 was identified by our study, in the compound heterozygous state with a variant of uncertain significance (ClinVar Variation ID: … (more)
The heterozygous p.Pro632PhefsTer7 variant in BBS12 was identified by our study, in the compound heterozygous state with a variant of uncertain significance (ClinVar Variation ID: 444641), in one individual with cone-rod dystrophy. This individual also carried a variant of uncertain significance (ClinVar Variation ID: 444641), however the phase of these variants are unknown at this time. The p.Pro632PhefsTer7 variant in BBS12 has been previously reported in 5 unrelated individuals with Bardet-Biedl syndrome 12 (PMID: 30614526, PMID: 33532864, PMID: 20472660, PMID: 17160889) but has been identified in 0.0009% (1/113452) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs765915863). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. Of these 5 previously reported unrelated individuals (PMID: 30614526, PMID: 33532864, PMID: 20472660, PMID: 17160889), one was a compound heterozygote who carried a likely pathogenic variant in trans (PMID: 30614526, ClinVar Variation ID: 1151) and four were compound heterozygotes who carried variants of uncertain significance in trans (PMID: 33532864, PMID: 20472660, ClinVar Variation ID: ClinVar ID 974416; PMID: 17160889, NC_000004.12:g.122743410_122743412del, NC_000004.12:g.122743671_122743672insA), which increases the likelihood that the p.Pro632PhefsTer7 variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 866623) and has been interpreted as pathogenic or likely pathogenic by multiple submitters. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 632 and leads to a premature termination codon 7 amino acids downstream. This termination codon occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Loss of function of the BBS12 gene is an established disease mechanism in autosomal recessive Bardet-Biedl syndrome 12. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive Bardet-Biedl syndrome 12. ACMG/AMP Criteria applied: PVS1_Moderate, PM2_Supporting, PM3_Strong (Richards 2015). (less)
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Pathogenic
(Feb 10, 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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Baylor Genetics
Accession: SCV004213976.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 06, 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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Invitae
Accession: SCV001411126.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Pro632Phefs*7) 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.Pro632Phefs*7) in the BBS12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 79 amino acid(s) of the BBS12 protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 17160889, 20472660). This variant is also known as 1890delCT. ClinVar contains an entry for this variant (Variation ID: 866623). This variant disrupts a region of the BBS12 protein in which other variant(s) (p.Arg675*) have been determined to be pathogenic (PMID: 20827784, 21642631). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 31, 2024)
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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: SCV004730880.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The BBS12 c.1893_1894delTC variant is predicted to result in a frameshift and premature protein termination (p.Pro632Phefs*7). This variant has been reported in the compound heterozygous … (more)
The BBS12 c.1893_1894delTC variant is predicted to result in a frameshift and premature protein termination (p.Pro632Phefs*7). This variant has been reported in the compound heterozygous state in patients with Bardet-Biedl syndrome (referred to as c.1890delCT in Stoetzel et al. 2007. PubMed ID: 17160889; Billingsley et al. 2010. PubMed ID: 20472660; Deveault et al. 2011. PubMed ID: 21344540). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in BBS12 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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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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Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players. | Domingo-Gallego A | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2022 | PMID: 33532864 |
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 |
Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population. | Billingsley G | Journal of medical genetics | 2010 | PMID: 20472660 |
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 |
- | - | - | - | DOI: doi:10.1155/2023/2564200 |
Text-mined citations for rs1560708847 ...
HelpRecord last updated Mar 30, 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.