ClinVar Genomic variation as it relates to human health
NM_007294.3(BRCA1):c.[594-2A>C;641A>G]
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
NM_007294.3(BRCA1):c.[594-2A>C;641A>G]
- Other names
- -
- Functional consequence
- -
- Links
- ClinGen: CA645372626
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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BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
12795 | 14565 |
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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Benign (1) |
reviewed by expert panel
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Apr 15, 2016 | RCV000225499.11 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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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Benign
(Apr 15, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282252.1
First in ClinVar: Jun 25, 2016 Last updated: Jun 25, 2016 |
Comment:
IARC class based on combined odds from multifactorial likelihood analysis, thresholds for class as per Easton et al. 2007 (PMID: 17924331). Class 1 Not Pathogenic … (more)
IARC class based on combined odds from multifactorial likelihood analysis, thresholds for class as per Easton et al. 2007 (PMID: 17924331). Class 1 Not Pathogenic based on combined odds = 3.23x10-8. Variant allele produces 70-80% predicted non-functional transcripts and 20-30% of predicted functional r.548_670del transcript. (less)
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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 germline mutational landscape of genitourinary cancers and its indication for prognosis and risk. | Yang Y | BMC urology | 2022 | PMID: 36451132 |
Under-ascertainment of breast cancer susceptibility gene carriers in a cohort of New Zealand female breast cancer patients. | Lattimore V | Breast cancer research and treatment | 2021 | PMID: 33113089 |
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 |
Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer. | Karam R | JAMA network open | 2019 | PMID: 31642931 |
Outcome of Pancreatic Cancer Surveillance Among High-Risk Individuals Tested for Germline Mutations in BRCA1 and BRCA2. | Saldia A | Cancer prevention research (Philadelphia, Pa.) | 2019 | PMID: 31337648 |
Targeted RNA-seq successfully identifies normal and pathogenic splicing events in breast/ovarian cancer susceptibility and Lynch syndrome genes. | Brandão RD | International journal of cancer | 2019 | PMID: 30623411 |
The impact of variant classification on the clinical management of hereditary cancer syndromes. | Turner SA | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29875428 |
A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function. | Starita LM | American journal of human genetics | 2018 | PMID: 30219179 |
Investigation of Experimental Factors That Underlie BRCA1/2 mRNA Isoform Expression Variation: Recommendations for Utilizing Targeted RNA Sequencing to Evaluate Potential Spliceogenic Variants. | Lattimore VL | Frontiers in oncology | 2018 | PMID: 29774201 |
Investigation of Experimental Factors That Underlie BRCA1/2 mRNA Isoform Expression Variation: Recommendations for Utilizing Targeted RNA Sequencing to Evaluate Potential Spliceogenic Variants. | Lattimore VL | Frontiers in oncology | 2018 | PMID: 29774201 |
A Danish national effort of BRCA1/2 variant classification. | Pedersen IS | Acta oncologica (Stockholm, Sweden) | 2018 | PMID: 29168416 |
Detection of BRCA1/2 mutations in circulating tumor DNA from patients with ovarian cancer. | Ratajska M | Oncotarget | 2017 | PMID: 29254167 |
Detection of BRCA1/2 mutations in circulating tumor DNA from patients with ovarian cancer. | Ratajska M | Oncotarget | 2017 | PMID: 29254167 |
Consistency of BRCA1 and BRCA2 Variant Classifications Among Clinical Diagnostic Laboratories. | Lincoln SE | JCO precision oncology | 2017 | PMID: 28782058 |
Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma. | Shindo K | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2017 | PMID: 28767289 |
Recontacting in clinical practice: an investigation of the views of healthcare professionals and clinical scientists in the United Kingdom. | Carrieri D | European journal of human genetics : EJHG | 2017 | PMID: 28051074 |
Germline Analysis from Tumor-Germline Sequencing Dyads to Identify Clinically Actionable Secondary Findings. | Seifert BA | Clinical cancer research : an official journal of the American Association for Cancer Research | 2016 | PMID: 27083775 |
Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms. | de la Hoya M | Human molecular genetics | 2016 | PMID: 27008870 |
Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms. | de la Hoya M | Human molecular genetics | 2016 | PMID: 27008870 |
Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms. | de la Hoya M | Human molecular genetics | 2016 | PMID: 27008870 |
Adding In Silico Assessment of Potential Splice Aberration to the Integrated Evaluation of BRCA Gene Unclassified Variants. | Vallée MP | Human mutation | 2016 | PMID: 26913838 |
When is a mutation not a mutation: the case of the c.594-2A>C splice variant in a woman harbouring another BRCA1 mutation in trans. | Wong-Brown M | Hereditary cancer in clinical practice | 2016 | PMID: 26884819 |
When is a mutation not a mutation: the case of the c.594-2A>C splice variant in a woman harbouring another BRCA1 mutation in trans. | Wong-Brown M | Hereditary cancer in clinical practice | 2016 | PMID: 26884819 |
Panel Testing for Familial Breast Cancer: Calibrating the Tension Between Research and Clinical Care. | Thompson ER | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2016 | PMID: 26786923 |
Genetic testing in a cohort of young patients with HER2-amplified breast cancer. | Eccles DM | Annals of oncology : official journal of the European Society for Medical Oncology | 2016 | PMID: 26681682 |
Patterns and functional implications of rare germline variants across 12 cancer types. | Lu C | Nature communications | 2015 | PMID: 26689913 |
A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Genes in More Than 1000 Patients. | Lincoln SE | The Journal of molecular diagnostics : JMD | 2015 | PMID: 26207792 |
Exceptions to the rule: case studies in the prediction of pathogenicity for genetic variants in hereditary cancer genes. | Rosenthal ET | Clinical genetics | 2015 | PMID: 25639900 |
Exceptions to the rule: case studies in the prediction of pathogenicity for genetic variants in hereditary cancer genes. | Rosenthal ET | Clinical genetics | 2015 | PMID: 25639900 |
Mutational analysis of BRCA1/2 in a group of 134 consecutive ovarian cancer patients. Novel and recurrent BRCA1/2 alterations detected by next generation sequencing. | Ratajska M | Journal of applied genetics | 2015 | PMID: 25366421 |
Functional characterization of BRCA1 gene variants by mini-gene splicing assay. | Steffensen AY | European journal of human genetics : EJHG | 2014 | PMID: 24667779 |
Comprehensive annotation of splice junctions supports pervasive alternative splicing at the BRCA1 locus: a report from the ENIGMA consortium. | Colombo M | Human molecular genetics | 2014 | PMID: 24569164 |
Comparison of mRNA splicing assay protocols across multiple laboratories: recommendations for best practice in standardized clinical testing. | Whiley PJ | Clinical chemistry | 2014 | PMID: 24212087 |
BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. | Pennington KP | Cancer | 2013 | PMID: 22811390 |
BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. | Pennington KP | Cancer | 2013 | PMID: 22811390 |
Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction. | Wappenschmidt B | PloS one | 2012 | PMID: 23239986 |
BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. | Alsop K | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2012 | PMID: 22711857 |
A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes. | Hondow HL | BMC cancer | 2011 | PMID: 21702907 |
A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes. | Hondow HL | BMC cancer | 2011 | PMID: 21702907 |
Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling. | Capanu M | Genetic epidemiology | 2011 | PMID: 21520273 |
Prediction of single-nucleotide substitutions that result in exon skipping: identification of a splicing silencer in BRCA1 exon 6. | Raponi M | Human mutation | 2011 | PMID: 21309043 |
Genetic diagnosis of familial breast cancer using clonal sequencing. | Morgan JE | Human mutation | 2010 | PMID: 20127978 |
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
Alternative splicing and molecular characterization of splice site variants: BRCA1 c.591C>T as a case study. | Dosil V | Clinical chemistry | 2010 | PMID: 19892845 |
Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years. | Malone KE | Cancer research | 2006 | PMID: 16912212 |
A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. | van der Hout AH | Human mutation | 2006 | PMID: 16683254 |
A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. | van der Hout AH | Human mutation | 2006 | PMID: 16683254 |
Molecular characterization and cancer risk associated with BRCA1 and BRCA2 splice site variants identified in multiple-case breast cancer families. | Tesoriero AA | Human mutation | 2005 | PMID: 16211554 |
Molecular characterization and cancer risk associated with BRCA1 and BRCA2 splice site variants identified in multiple-case breast cancer families. | Tesoriero AA | Human mutation | 2005 | PMID: 16211554 |
Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. | Pavlicek A | Human molecular genetics | 2004 | PMID: 15385441 |
Average age-specific cumulative risk of breast cancer according to type and site of germline mutations in BRCA1 and BRCA2 estimated from multiple-case breast cancer families attending Australian family cancer clinics. | Scott CL | Human genetics | 2003 | PMID: 12601471 |
The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer. | Southey MC | British journal of cancer | 1999 | PMID: 10408690 |
BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer. | Southey MC | British journal of cancer | 1999 | PMID: 10408690 |
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Text-mined citations for this variant ...
HelpRecord last updated Apr 20, 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.