ClinVar Genomic variation as it relates to human health
NM_000465.4(BARD1):c.159-1G>T
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_000465.4(BARD1):c.159-1G>T
Variation ID: 246176 Accession: VCV000246176.38
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 214797118 (GRCh38) [ NCBI UCSC ] 2: 215661842 (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 Jul 25, 2016 May 1, 2024 Nov 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000465.4:c.159-1G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001282543.2:c.159-4673G>T intron variant NM_001282545.2:c.159-1G>T splice acceptor NM_001282548.2:c.158+12294G>T intron variant NM_001282549.2:c.159-1G>T splice acceptor NC_000002.12:g.214797118C>A NC_000002.11:g.215661842C>A NG_012047.3:g.17594G>T LRG_297:g.17594G>T LRG_297t1:c.159-1G>T - Protein change
- Other names
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- Canonical SPDI
- NC_000002.12:214797117:C:A
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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
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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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BARD1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3939 | 3993 |
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
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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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jun 14, 2023 | RCV000235953.12 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Nov 28, 2023 | RCV000552182.20 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 27, 2023 | RCV000565922.16 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 7, 2017 | RCV000587901.4 |
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
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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
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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
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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
(Feb 07, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696749.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The BARD1 c.159-1G>T variant involves the alteration of a conserved intronic nucleotide. Mutation Taster predicts a damaging outcome for this variant. 4/5 splice … (more)
Variant summary: The BARD1 c.159-1G>T variant involves the alteration of a conserved intronic nucleotide. Mutation Taster predicts a damaging outcome for this variant. 4/5 splice prediction tools predict a significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 121314 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, however, a clinical diagnostic laboratory classified this variant as likely pathogenic. Taken together, this variant is classified as likely pathogenic. (less)
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Pathogenic
(Aug 09, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000688135.5
First in ClinVar: Feb 19, 2018 Last updated: Jan 08, 2022 |
Comment:
This variant causes a G to T nucleotide substitution at the -1 position of intron 1 of the BARD1 gene. An RNA study has reported … (more)
This variant causes a G to T nucleotide substitution at the -1 position of intron 1 of the BARD1 gene. An RNA study has reported two aberrant transcripts found uniquely in carrier and absent in healthy control that are expected to produce absent or non-functional protein product (PMID: 31843900). This variant also has been reported in one individual each affected with breast and ovarian cancer (PMID: 31036035, 31843900). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BARD1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Likely pathogenic
(Nov 22, 2022)
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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: SCV000293620.11
First in ClinVar: Jul 25, 2016 Last updated: Dec 03, 2022 |
Comment:
Canonical splice site variant expected to result in aberrant splicing; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a … (more)
Canonical splice site variant expected to result in aberrant splicing; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect: abnormal splicing (Casadei et al., 2019); This variant is associated with the following publications: (PMID: 31843900, 31036035, 33804961, 33809641) (less)
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Pathogenic
(Nov 24, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002814602.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV003804664.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Comment:
_x000D_ Criteria applied: PVS1, PS4_MOD, PM2_SUP
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Likely pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV004026029.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
Comment:
PVS1
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Likely pathogenic
(May 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004044203.2
First in ClinVar: Oct 21, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either … (more)
This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. (less)
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Likely pathogenic
(Aug 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004217203.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004221609.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
The BARD1 c.159-1G>T variant disrupts a canonical splice-acceptor site and interferes with normal BARD1 mRNA splicing. This variant has been reported in the published literature … (more)
The BARD1 c.159-1G>T variant disrupts a canonical splice-acceptor site and interferes with normal BARD1 mRNA splicing. This variant has been reported in the published literature in affected individuals with breast cancer (PMIDs: 31036035 (2019) and 33471991 (2021)), ovarian and prostate cancer (PMID: 31843900 (2019)), b-cell neoplasms (PMID: 33809641 (2021)), as well as in a healthy individual (PMID: 33471991 (2021)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Nov 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000632971.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 1 of the BARD1 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 1 of the BARD1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer, ovarian or prostate cancer (PMID: 31036035, 31843900). ClinVar contains an entry for this variant (Variation ID: 246176). Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (PMID: 31843900; Invitae). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 01, 2022)
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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: SCV002822789.8
First in ClinVar: Jan 21, 2023 Last updated: Apr 15, 2024 |
Comment:
BARD1: PVS1, PM2
Number of individuals with the variant: 1
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Likely pathogenic
(Jun 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000660810.7
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The c.159-1G>T intronic variant results from a G to T substitution one nucleotide upstream from coding exon 2 of the BARD1 gene. In one study, … (more)
The c.159-1G>T intronic variant results from a G to T substitution one nucleotide upstream from coding exon 2 of the BARD1 gene. In one study, this alteration was detected in 1/4469 German breast cancer patients (Weber-Lassalle N et al. Breast Cancer Res., 2019 04;21:55). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). A published RNA study also identified abnormal splicing associated with this variant (Casadei S et al. Proc Natl Acad Sci U S A, 2019 Dec). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. (less)
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Pathogenic
(Sep 01, 2019)
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no assertion criteria provided
Method: research
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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King Laboratory, University of Washington
Accession: SCV001251317.1
First in ClinVar: Jun 07, 2020 Last updated: Jun 07, 2020
Comment:
Transcript analysis by cBROCA
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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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Detection of Rare Germline Variants in the Genomes of Patients with B-Cell Neoplasms. | Mosquera Orgueira A | Cancers | 2021 | PMID: 33809641 |
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Characterization of splice-altering mutations in inherited predisposition to cancer. | Casadei S | Proceedings of the National Academy of Sciences of the United States of America | 2019 | PMID: 31843900 |
Germline loss-of-function variants in the BARD1 gene are associated with early-onset familial breast cancer but not ovarian cancer. | Weber-Lassalle N | Breast cancer research : BCR | 2019 | PMID: 31036035 |
Cancer predisposing BARD1 mutations in breast-ovarian cancer families. | Ratajska M | Breast cancer research and treatment | 2012 | PMID: 21344236 |
Cancer predisposing missense and protein truncating BARD1 mutations in non-BRCA1 or BRCA2 breast cancer families. | De Brakeleer S | Human mutation | 2010 | PMID: 20077502 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Text-mined citations for rs879254139 ...
HelpRecord last updated May 08, 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.