ClinVar Genomic variation as it relates to human health
NM_024685.4(BBS10):c.728_731del (p.Lys243fs)
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_024685.4(BBS10):c.728_731del (p.Lys243fs)
Variation ID: 189071 Accession: VCV000189071.33
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 12q21.2 12: 76347254-76347257 (GRCh38) [ NCBI UCSC ] 12: 76741034-76741037 (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 29, 2015 May 26, 2024 May 18, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_024685.4:c.728_731del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_078961.3:p.Lys243fs frameshift NC_000012.12:g.76347257_76347260del NC_000012.11:g.76741037_76741040del NG_016357.1:g.6186_6189del LRG_1255:g.6186_6189del LRG_1255t1:c.728_731del LRG_1255p1:p.Lys243fs - Protein change
- K243fs
- Other names
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- Canonical SPDI
- NC_000012.12:76347253:TCTTTCT:TCT
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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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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
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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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BBS10 | - | - |
GRCh38 GRCh37 |
866 | 880 |
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/Likely pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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May 18, 2024 | RCV000169474.14 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 5, 2023 | RCV000638365.9 |
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
(Nov 25, 2014)
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criteria provided, single submitter
Method: literature only
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Bardet-Biedl syndrome 10
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220920.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Jun 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 10
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004217450.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 10
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV001752436.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021
Comment:
This variant has been detected in individual(s) who were sent for testing of Renasight - kidney gene panel.
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 10
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002058552.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated … (more)
Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_S). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000189071, PMID:16582908). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Blindness (present) , Global developmental delay (present) , Intellectual disability (present) , Obesity (present) , Seizure (present)
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Pathogenic
(Sep 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 10
Affected status: yes
Allele origin:
germline
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Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV003807890.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Comment:
ACMG classification criteria: PVS1 strong, PS4 moderated, PM2 moderated, PM3 moderated
Number of individuals with the variant: 1
Clinical Features:
Postaxial foot polydactyly (present) , Epicanthus (present) , Obesity (present) , Bilateral cryptorchidism (present) , Polycystic kidney disease (present) , Increased body weight (present) , … (more)
Postaxial foot polydactyly (present) , Epicanthus (present) , Obesity (present) , Bilateral cryptorchidism (present) , Polycystic kidney disease (present) , Increased body weight (present) , Postaxial hand polydactyly (present) (less)
Geographic origin: Brazil
Method: Paired-end whole-genome sequencing
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Pathogenic
(Jul 01, 2023)
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criteria provided, single submitter
Method: research
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Bardet-Biedl syndrome
Affected status: yes
Allele origin:
germline
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Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand
Accession: SCV004123099.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
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Pathogenic
(Oct 05, 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: SCV000759864.4
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Lys243Ilefs*15) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Lys243Ilefs*15) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 481 amino acid(s) of the BBS10 protein. This variant is present in population databases (rs786204671, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 16582908, 17106446, 22353939, 22773737, 24041679, 27245532). It is commonly reported in individuals of South African ancestry (PMID: 16582908, 17106446, 22353939, 22773737, 24041679, 27245532). This variant is also known as c.995_999delAAGA (p.Q242fs258X). ClinVar contains an entry for this variant (Variation ID: 189071). This variant disrupts a region of the BBS10 protein in which other variant(s) (p.Gly677Valfs*5, p.Val707*) have been determined to be pathogenic (PMID: 20472660, 22773737, 25982971, 27486776; Invitae). 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
(Mar 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 10
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004808170.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(May 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 10
Affected status: yes
Allele origin:
germline
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV005044663.1
First in ClinVar: May 26, 2024 Last updated: May 26, 2024 |
Sex: male
Geographic origin: Iran
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Pathogenic
(Sep 16, 2021)
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no assertion criteria provided
Method: clinical testing
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Bardet-Biedl syndrome type 10
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002091783.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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: SCV000839564.1 First in ClinVar: May 28, 2018 Last updated: May 28, 2018 |
Age: 20-29 weeks gestation
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Pathogenic
(Apr 01, 2023)
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no assertion criteria provided
Method: clinical testing
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Bardet-Biedl syndrome 10
Affected status: yes
Allele origin:
germline
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Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)
Accession: SCV003927959.1
First in ClinVar: Sep 16, 2023 Last updated: Sep 16, 2023 |
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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 |
Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome. | Lindstrand A | American journal of human genetics | 2016 | PMID: 27486776 |
Bardet Biedl syndrome in South Africa: A single founder mutation. | Fieggen K | South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde | 2016 | PMID: 27245532 |
Predominantly Cone-System Dysfunction as Rare Form of Retinal Degeneration in Patients With Molecularly Confirmed Bardet-Biedl Syndrome. | Scheidecker S | American journal of ophthalmology | 2015 | PMID: 25982971 |
Highly sensitive diagnosis of 43 monogenic forms of diabetes or obesity through one-step PCR-based enrichment in combination with next-generation sequencing. | Bonnefond A | Diabetes care | 2014 | PMID: 24041679 |
Targeted high-throughput sequencing for diagnosis of genetically heterogeneous diseases: efficient mutation detection in Bardet-Biedl and Alström syndromes. | Redin C | Journal of medical genetics | 2012 | PMID: 22773737 |
In search of triallelism in Bardet-Biedl syndrome. | Abu-Safieh L | European journal of human genetics : EJHG | 2012 | PMID: 22353939 |
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 |
Autozygosity mapping of Bardet-Biedl syndrome to 12q21.2 and confirmation of FLJ23560 as BBS10. | White DR | European journal of human genetics : EJHG | 2007 | PMID: 17106446 |
BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. | Stoetzel C | Nature genetics | 2006 | PMID: 16582908 |
Text-mined citations for rs786204671 ...
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.