ClinVar Genomic variation as it relates to human health
NM_001122955.4(BSCL2):c.1280T>C (p.Leu427Pro)
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.
Uncertain risk allele(1); Benign(4); Likely benign(9)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001122955.4(BSCL2):c.1280T>C (p.Leu427Pro)
Variation ID: 128532 Accession: VCV000128532.61
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q12.3 11: 62690476 (GRCh38) [ NCBI UCSC ] 11: 62457948 (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 Aug 4, 2024 Apr 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001122955.4:c.1280T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001116427.1:p.Leu427Pro missense NM_001130702.2:c.*82T>C 3 prime UTR NM_001386027.1:c.1286T>C NP_001372956.1:p.Leu429Pro missense NM_001386028.1:c.1280T>C NP_001372957.1:p.Leu427Pro missense NM_032667.6:c.1088T>C NP_116056.3:p.Leu363Pro missense NR_037946.1:n.3800T>C non-coding transcript variant NC_000011.10:g.62690476A>G NC_000011.9:g.62457948A>G NG_008461.1:g.24099T>C NG_033077.1:g.4424T>C LRG_235:g.24099T>C LRG_235t1:c.1280T>C LRG_235p1:p.Leu427Pro LRG_235t2:c.1088T>C LRG_235p2:p.Leu363Pro - Protein change
- L427P, L363P, L429P
- Other names
- -
- Canonical SPDI
- NC_000011.10:62690475:A:G
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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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0.00080 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00080
1000 Genomes Project 30x 0.00094
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00261
The Genome Aggregation Database (gnomAD) 0.00301
Trans-Omics for Precision Medicine (TOPMed) 0.00306
The Genome Aggregation Database (gnomAD), exomes 0.00352
Exome Aggregation Consortium (ExAC) 0.00392
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
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
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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BSCL2 | - | - |
GRCh38 GRCh37 |
5 | 567 | |
HNRNPUL2-BSCL2 | - | - | - | GRCh38 | - | 600 |
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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Benign/Likely benign (8) |
criteria provided, multiple submitters, no conflicts
|
Apr 1, 2024 | RCV000116504.44 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
May 23, 2017 | RCV000174173.21 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 13, 2018 | RCV000300263.14 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV000357438.13 | |
Benign (1) |
criteria provided, single submitter
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Aug 10, 2018 | RCV000664139.11 | |
Benign (1) |
criteria provided, single submitter
|
Feb 1, 2024 | RCV001082147.15 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 16, 2021 | RCV001847675.11 | |
Likely benign (1) |
criteria provided, single submitter
|
May 18, 2020 | RCV002426660.9 | |
Likely benign (1) |
criteria provided, single submitter
|
Oct 14, 2021 | RCV002498501.8 |
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 benign
(Feb 27, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000225428.5
First in ClinVar: Jun 28, 2015 Last updated: Apr 09, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(Jan 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV001145759.1
First in ClinVar: Jan 18, 2020 Last updated: Jan 18, 2020 |
|
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Likely benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital generalized lipodystrophy type 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000372861.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Likely benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Neuronopathy, distal hereditary motor, type 5A
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000372862.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Likely benign
(Aug 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, The Hospital for Sick Children
Accession: SCV002106246.1
First in ClinVar: Mar 19, 2022 Last updated: Mar 19, 2022 |
|
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Likely benign
(May 18, 2020)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002726888.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
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Likely benign
(May 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000150452.2
First in ClinVar: May 17, 2014 Last updated: Nov 10, 2017 |
|
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Benign
(Aug 10, 2018)
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criteria provided, single submitter
Method: research
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Monogenic diabetes
Affected status: unknown
Allele origin:
unknown
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Personalized Diabetes Medicine Program, University of Maryland School of Medicine
Accession: SCV000787591.2
First in ClinVar: Jul 21, 2018 Last updated: Jun 13, 2020 |
Comment:
ACMG criteria: BS1 (0.7% in gnomAD AJ population, 0.3% overall MAF in gnomAD; disease prevalence 1:10 million gives MAF of 0.03%), BS2 (3 homozygotes in … (more)
ACMG criteria: BS1 (0.7% in gnomAD AJ population, 0.3% overall MAF in gnomAD; disease prevalence 1:10 million gives MAF of 0.03%), BS2 (3 homozygotes in gnomAD ENF pop) [REVEL 0.257, PP3 (4 predictors), BP4 (6 predictors)= conflicting evidence, not using]= benign (less)
Number of individuals with the variant: 2
|
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Likely benign
(Mar 25, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885126.2
First in ClinVar: Nov 10, 2017 Last updated: Jan 08, 2022 |
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Likely benign
(Oct 14, 2021)
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criteria provided, single submitter
Method: clinical testing
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Congenital generalized lipodystrophy type 2
Hereditary spastic paraplegia 17 Severe neurodegenerative syndrome with lipodystrophy Neuronopathy, distal hereditary motor, type 5C
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002804276.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Apr 09, 2019)
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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: SCV000278907.7
First in ClinVar: May 29, 2016 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 29482223, 33111339)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Charcot-Marie-Tooth disease type 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000259514.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
|
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Likely benign
(Apr 01, 2024)
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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: SCV000493255.31
First in ClinVar: May 17, 2014 Last updated: Aug 04, 2024 |
Comment:
BSCL2: BS2
Number of individuals with the variant: 23
|
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Uncertain risk allele
(-)
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criteria provided, single submitter
Method: research
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Congenital generalized lipodystrophy type 2
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV004698134.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
Comment:
Potent mutations in BSCL2 gene are associated with Congenital generalized lipodystrophy, type 2, which can present with insulin resistance, fatty liver and diabetes.However, the role … (more)
Potent mutations in BSCL2 gene are associated with Congenital generalized lipodystrophy, type 2, which can present with insulin resistance, fatty liver and diabetes.However, the role of this particular variant rs145649423 of Congenital Generalized Lipodystrophy type 2 remains uncertain (less)
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Likely benign
(-)
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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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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001740387.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Likely benign
(-)
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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, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001925536.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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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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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001928844.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
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: SCV001971798.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 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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The neonatal onset diabetes mellitus of Chinese neonate with congenital generalized lipodystrophy 2: a case report. | Yang Y | BMC endocrine disorders | 2022 | PMID: 35351089 |
A New Compound Heterozygous Mutation Of BSCL2 In A Chinese Zhuang Ethnic Family With Congenital Generalized Lipodystrophy. | Qin YY | Diabetes, metabolic syndrome and obesity : targets and therapy | 2019 | PMID: 31824185 |
Investigation of next-generation sequencing technologies as a diagnostic tool for amyotrophic lateral sclerosis. | Morgan S | Neurobiology of aging | 2015 | PMID: 25588603 |
Targeted next-generation sequencing reveals further genetic heterogeneity in axonal Charcot-Marie-Tooth neuropathy and a mutation in HSPB1. | Ylikallio E | European journal of human genetics : EJHG | 2014 | PMID: 23963299 |
Congenital generalized lipodystrophy in an Indian patient with a novel mutation in BSCL2 gene. | Shirwalkar HU | Journal of inherited metabolic disease | 2008 | PMID: 18690553 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BSCL2 | - | - | - | - |
Text-mined citations for rs145649423 ...
HelpRecord last updated Aug 25, 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.