ClinVar Genomic variation as it relates to human health
NM_000465.4(BARD1):c.334C>T (p.Arg112Ter)
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.334C>T (p.Arg112Ter)
Variation ID: 185139 Accession: VCV000185139.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 214792327 (GRCh38) [ NCBI UCSC ] 2: 215657051 (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 Jan 9, 2017 May 1, 2024 Dec 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000465.4:c.334C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000456.2:p.Arg112Ter nonsense NM_001282543.2:c.277C>T NP_001269472.1:p.Arg93Ter nonsense NM_001282545.2:c.215+4734C>T intron variant NM_001282548.2:c.158+17085C>T intron variant NM_001282549.2:c.334C>T NP_001269478.1:p.Arg112Ter nonsense NR_104216.2:n.448C>T non-coding transcript variant NC_000002.12:g.214792327G>A NC_000002.11:g.215657051G>A NG_012047.3:g.22385C>T LRG_297:g.22385C>T LRG_297t1:c.334C>T LRG_297p1:p.Arg112Ter - Protein change
- R112*, R93*
- Other names
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- Canonical SPDI
- NC_000002.12:214792326:G: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.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
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 |
3943 | 3997 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Aug 3, 2022 | RCV000164507.9 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Dec 22, 2023 | RCV000233846.15 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 24, 2022 | RCV000413073.5 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 11, 2019 | RCV001270959.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 15, 2022 | RCV002281980.1 |
Submissions - Germline
Classification
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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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Pathogenic
(Jan 15, 2020)
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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: SCV001357309.2
First in ClinVar: Mar 25, 2020 Last updated: Jan 12, 2022 |
Comment:
This variant changes 1 nucleotide in exon 3 of the BARD1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 3 of the BARD1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 2/251010 chromosomes 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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Pathogenic
(Jul 15, 2022)
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criteria provided, single submitter
Method: clinical testing
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Malignant tumor of breast
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002570611.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: BARD1 c.334C>T (p.Arg112X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BARD1 c.334C>T (p.Arg112X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.5e-05 in 259978 control chromosomes (gnomAD and Palmer_2020). c.334C>T has been reported in the literature in multiple individuals affected with breast cancer (e.g. Gonzalez-Rivera_ 2016, Tavera-Tapia_2017, Sun_2017, Weber-Lassalle_2019) and in individuals with neuroblastoma and ovarian cancer (e.g.Pugh_2013, Lilyquist_2017). These data indicate that the variant is likely to be associated with disease. Four clinical diagnostic laboratories and a professional group (CZECANCA consortium) have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Aug 26, 2021)
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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: SCV002774306.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
This nonsense variant causes the premature termination of BARD1 protein synthesis. It has been described in individuals with breast cancer and neuroblastoma in the published … (more)
This nonsense variant causes the premature termination of BARD1 protein synthesis. It has been described in individuals with breast cancer and neuroblastoma in the published literature (PMIDs: 31036035 (2019), 30781715 (2019), 28724667 (2017), 27083178 (2016), and 23334666 (2013)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jun 24, 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: SCV000490424.6
First in ClinVar: Jan 09, 2017 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); Observed in individuals with breast cancer, ovarian cancer, or neuroblastoma (Pugh 2013, Gonzalez-Rivera 2016, Sun 2017, Weber-Lassalle 2019, Suszynska 2020); This variant is associated with the following publications: (PMID: 23334666, 28985766, 27083178, 28055978, 28152038, 28724667, 29292755, 31036035, 32679805, 27535533, 32427313) (less)
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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: SCV004044112.2
First in ClinVar: Oct 21, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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Pathogenic
(Apr 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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Baylor Genetics
Accession: SCV004217287.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 22, 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: SCV000284955.11
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg112*) in the BARD1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg112*) in the BARD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236). This variant is present in population databases (rs758972589, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with neuroblastoma (PMID: 23334666, 27083178). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 185139). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 03, 2022)
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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: SCV000215158.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.R112* pathogenic mutation (also known as c.334C>T), located in coding exon 3 of the BARD1 gene, results from a C to T substitution at … (more)
The p.R112* pathogenic mutation (also known as c.334C>T), located in coding exon 3 of the BARD1 gene, results from a C to T substitution at nucleotide position 334. This changes the amino acid from an arginine to a stop codon within coding exon 3. This alteration was detected in a cohort of 8085 consecutive unselected Chinese breast cancer patients who underwent multi-gene panel testing (Sun L et al. Clin. Cancer Res. 2017 Oct;23(20):6113-6119), and has been reported in 1 of 124 patients with stage II-III triple negative breast cancer (González-Rivera M et al. Breast Cancer Res. Treat. 2016 Apr;156:507-515). This alteration has also been reported as a germline mutation in a cohort of patients with neuroblastoma tumors (Pugh TJ et al. Nat. Genet. 2013 Mar; 45(3):279-84. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jun 11, 2019)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
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CZECANCA consortium
Accession: SCV001451763.1
First in ClinVar: Dec 24, 2020 Last updated: Dec 24, 2020 |
Number of individuals with the variant: 1
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
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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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Summary of BARD1 Mutations and Precise Estimation of Breast and Ovarian Cancer Risks Associated with the Mutations. | Suszynska M | Genes | 2020 | PMID: 32679805 |
Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women. | Palmer JR | Journal of the National Cancer Institute | 2020 | PMID: 32427313 |
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 |
Genetic Epidemiology of Breast Cancer in Latin America. | Zavala VA | Genes | 2019 | PMID: 30781715 |
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer. | Hu C | JAMA | 2018 | PMID: 29922827 |
Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. | Lilyquist J | Gynecologic oncology | 2017 | PMID: 28888541 |
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene. | Tavera-Tapia A | Breast cancer research and treatment | 2017 | PMID: 27913932 |
Frequency of germline DNA genetic findings in an unselected prospective cohort of triple-negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial. | González-Rivera M | Breast cancer research and treatment | 2016 | PMID: 27083178 |
The genetic landscape of high-risk neuroblastoma. | Pugh TJ | Nature genetics | 2013 | PMID: 23334666 |
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 |
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Text-mined citations for rs758972589 ...
HelpRecord last updated May 01, 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.