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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ClinVar Genomic variation as it relates to human health
NM_001079866.2(BCS1L):c.768C>G (p.Leu256=)
Germline
Classification
Help
criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.
Conflicting classifications of pathogenicity
Uncertain significance(3); Likely benign(2)
Uncertain significance(3); Likely benign(2)
5 out of 6 submissions contributed to this classification
Help
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.
6
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001079866.2(BCS1L):c.768C>G (p.Leu256=)
Variation ID: 334359 Accession: VCV000334359.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 218662558 (GRCh38) [ NCBI UCSC ] 2: 219527281 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Feb 25, 2025 Feb 9, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001079866.2:c.768C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073335.1:p.Leu256= synonymous NM_001257342.2:c.768C>G NP_001244271.1:p.Leu256= synonymous NM_001257343.2:c.768C>G NP_001244272.1:p.Leu256= synonymous NM_001257344.2:c.768C>G NP_001244273.1:p.Leu256= synonymous NM_001318836.2:c.408C>G NP_001305765.1:p.Leu136= synonymous NM_001320717.2:c.768C>G NP_001307646.1:p.Leu256= synonymous NM_001371443.1:c.768C>G NP_001358372.1:p.Leu256= synonymous NM_001371444.1:c.768C>G NP_001358373.1:p.Leu256= synonymous NM_001371446.1:c.768C>G NP_001358375.1:p.Leu256= synonymous NM_001371447.1:c.768C>G NP_001358376.1:p.Leu256= synonymous NM_001371448.1:c.768C>G NP_001358377.1:p.Leu256= synonymous NM_001371449.1:c.768C>G NP_001358378.1:p.Leu256= synonymous NM_001371450.1:c.768C>G NP_001358379.1:p.Leu256= synonymous NM_001371451.1:c.408C>G NP_001358380.1:p.Leu136= synonymous NM_001371452.1:c.267C>G NP_001358381.1:p.Leu89= synonymous NM_001371453.1:c.267C>G NP_001358382.1:p.Leu89= synonymous NM_001371454.1:c.267C>G NP_001358383.1:p.Leu89= synonymous NM_001371455.1:c.267C>G NP_001358384.1:p.Leu89= synonymous NM_001371456.1:c.267C>G NP_001358385.1:p.Leu89= synonymous NM_001374085.1:c.768C>G NP_001361014.1:p.Leu256= synonymous NM_001374086.1:c.267C>G NP_001361015.1:p.Leu89= synonymous NM_004328.5:c.768C>G NP_004319.1:p.Leu256= synonymous NR_163955.1:n.1775C>G non-coding transcript variant NC_000002.12:g.218662558C>G NC_000002.11:g.219527281C>G NG_008018.1:g.7903C>G NG_033099.1:g.1983G>C LRG_539:g.7903C>G LRG_539t1:c.768C>G LRG_539p1:p.Leu256= - Protein change
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- Other names
- -
- Canonical SPDI
- NC_000002.12:218662557:C:G
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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
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00001
- 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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| BCS1L | Gene associated with autosomal recessive phenotype | No evidence available |
GRCh38 GRCh37 |
568 | 610 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV000279975.5 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV000338686.5 | |
| Uncertain significance (2) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV000394839.7 | |
| Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 9, 2024 | RCV000927961.12 |
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. |
Expand all rows
Collapse all rows
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Jan 12, 2018)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Mitochondrial complex III deficiency nuclear type 1 |
Illumina Laboratory Services, Illumina
Accession: SCV000427443.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
show
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Uncertain significance
(Jan 12, 2018)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Leigh syndrome |
Illumina Laboratory Services, Illumina
Accession: SCV000427441.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
show
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Uncertain significance
(Jan 12, 2018)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
GRACILE syndrome |
Illumina Laboratory Services, Illumina
Accession: SCV000427442.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
show
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Likely benign
(Sep 11, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Not Provided |
GeneDx
Accession: SCV001856810.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Likely benign
(Feb 09, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001073562.7
First in ClinVar: Dec 17, 2019 Last updated: Feb 25, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Likely benign
(Aug 05, 2020)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
GRACILE syndrome |
Natera, Inc.
Accession: SCV002076352.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
Comment:
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 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
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 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs781666793 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated May 17, 2025
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.