ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.2685_2686del (p.Pro897fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.2685_2686del (p.Pro897fs)
Variation ID: 54646 Accession: VCV000054646.24
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 17q21.31 17: 43092845-43092846 (GRCh38) [ NCBI UCSC ] 17: 41244862-41244863 (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 Apr 1, 2014 Jun 17, 2024 Sep 8, 2016 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- P850fs, P897fs, P770fs, P829fs, P849fs, P870fs, P871fs, P894fs, P729fs, P769fs, P855fs, P601fs, P785fs, P827fs, P856fs, P896fs, P786fs, P808fs, P809fs, P826fs, P830fs
- Other names
- 2804delAA
- Canonical SPDI
- NC_000017.11:43092844:TTT:T
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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
Help
The frequency of the allele represented by this VCV record.
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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
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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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BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
12940 | 14730 |
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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Pathogenic (14) |
reviewed by expert panel
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Sep 8, 2016 | RCV000077525.25 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 13, 2024 | RCV000504509.14 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 6, 2021 | RCV000510104.14 | |
Pathogenic (2) |
no assertion criteria provided
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- | RCV001353865.10 |
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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Pathogenic
(Sep 08, 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: SCV000299810.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Oct 10, 2014)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743411.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000325431.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Jan 05, 2017)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000677645.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Jan 13, 2024)
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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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Invitae
Accession: SCV001587212.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Pro897Lysfs*5) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Pro897Lysfs*5) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357636, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 9150151, 11597388, 16683254, 19949876, 24285858, 27767231). It is commonly reported in individuals of Dutch ancestry (PMID: 9150151, 11597388, 16683254). This variant is also known as 2804delAA. ClinVar contains an entry for this variant (Variation ID: 54646). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Accession: SCV005045956.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
PVS1; PM5_PTC_Strong
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Pathogenic
(Feb 21, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004217000.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(May 16, 2016)
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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: SCV000698973.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
Comment:
Variant summary: The BRCA1 c.2685_2686delAA (p.Pro897Lysfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense … (more)
Variant summary: The BRCA1 c.2685_2686delAA (p.Pro897Lysfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Mutation taster predicts a damaging outcome for this variant. The variant is absent in 121354 control chromosomes while it was reported in several HBOC patients indicating a deleterious impact. The variant is most prevalent in patients of Dutch origin and is known as a Dutch founder mutation (Peelen_AJHG_1997). Multiple clinical diagnostic laboratories/reputable databases classified this variant as Pathogenic. Taken together, this variant is classified as Pathogenic. (less)
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Pathogenic
(Sep 21, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744649.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Dec 29, 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: SCV000683055.2
First in ClinVar: Feb 19, 2018 Last updated: Mar 25, 2020 |
Comment:
This variant deletes 2 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 2 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in multiple individuals and families affected with breast, ovarian and fallopian tube cancer (PMID: 8807330, 9150151, 9361038, 9429140, 12354934, 14574155, 24285858) and has been reported as a Dutch founder mutation that is also common in Belgium (PMID: 9150151, 17591843, 23199084). This variant has been identified in 1/250904 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 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
(-)
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criteria provided, single submitter
Method: not provided
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University Hospital of Duesseldorf
Accession: SCV004171172.1
First in ClinVar: Dec 02, 2023 Last updated: Dec 02, 2023 |
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Pathogenic
(Oct 06, 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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Ambry Genetics
Accession: SCV000607768.5
First in ClinVar: Oct 23, 2017 Last updated: May 01, 2024 |
Comment:
The c.2685_2686delAA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 2685 to … (more)
The c.2685_2686delAA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 2685 to 2686, causing a translational frameshift with a predicted alternate stop codon (p.P897Kfs*5). This mutation has been reported in multiple hereditary breast and/or ovarian cancer families and has been reported as a Dutch founder mutation (Peelen T et al. Am. J. Hum. Genet., 1997 May;60:1041-9; Garvin AM et al. J Med Genet, 1997 Dec;34:990-5; Vehmanen P et al. Hum Mol Genet, 1997 Dec;6:2309-15; Verhoog LC et al. Eur J Cancer, 2001 Nov;37:2082-90; Piek JM et al. Fam Cancer, 2003;2:73-8; van der Hout AH et al. Hum Mutat, 2006 Jul;27:654-66; Vos JR et al. Cancer Epidemiol Biomarkers Prev, 2014 Nov;23:2482-91; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620; Haer-Wigman L et al. Eur J Hum Genet, 2019 02;27:325-330; Deng H et al. Mol Genet Genomic Med, 2019 06;7:e672). Of note, this alteration is also designated as 2804delAA and 2804_2805delAA in published literature. 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
(Jul 24, 2014)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
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Pathway Genomics
Accession: SCV000189893.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591405.2 First in ClinVar: Aug 28, 2017 Last updated: Apr 13, 2021 |
Comment:
The c.2685_2686delAA located within exon 11b of BRCA1 is a deletion type mutation, which is predicted to lead to frameshift and a premature stop codon … (more)
The c.2685_2686delAA located within exon 11b of BRCA1 is a deletion type mutation, which is predicted to lead to frameshift and a premature stop codon at position Pro897LysX5, and therefore resulting in truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in familial breast cancer patients. In summary, based on the above information, this variant is classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144512.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 25
Observation 2:
Number of individuals with the variant: 25
Geographic origin: Netherlands
Observation 3:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Geographic origin: Netherlands
Observation 4:
Number of individuals with the variant: 7
Ethnicity/Population group: Western European
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Pathogenic
(Jul 31, 2011)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000109326.3
First in ClinVar: Dec 23, 2013 Last updated: Oct 19, 2014 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
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: SCV000733637.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Mar 18, 2016)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745680.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(-)
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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 Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906157.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
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Pathogenic
(Mar 02, 2020)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV004244079.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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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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Comprehensive analysis of serum tumor markers and BRCA1/2 germline mutations in Chinese ovarian cancer patients. | Deng H | Molecular genetics & genomic medicine | 2019 | PMID: 30972954 |
1 in 38 individuals at risk of a dominant medically actionable disease. | Haer-Wigman L | European journal of human genetics : EJHG | 2019 | PMID: 30291343 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Novel BRCA1 and BRCA2 Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas. | Weren RD | Human mutation | 2017 | PMID: 27767231 |
Earlier Age of Breast Cancer Onset in Israeli BRCA Carriers-Is it a Real Phenomenon? | Agranat S | The breast journal | 2016 | PMID: 27533489 |
Variation in mutation spectrum partly explains regional differences in the breast cancer risk of female BRCA mutation carriers in the Netherlands. | Vos JR | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2014 | PMID: 25103822 |
Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. | Brohet RM | Journal of medical genetics | 2014 | PMID: 24285858 |
Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. | Janavičius R | The EPMA journal | 2010 | PMID: 23199084 |
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 |
Efficiency of BRCAPRO and Myriad II mutation probability thresholds versus cancer history criteria alone for BRCA1/2 mutation detection. | van Harssel JJ | Familial cancer | 2010 | PMID: 19949876 |
Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH. | Joosse SA | Breast cancer research and treatment | 2009 | PMID: 18704682 |
Founder mutations in BRCA1 and BRCA2 genes. | Ferla R | Annals of oncology : official journal of the European Society for Medical Oncology | 2007 | PMID: 17591843 |
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 |
Histopathological features of breast tumours in BRCA1, BRCA2 and mutation-negative breast cancer families. | Eerola H | Breast cancer research : BCR | 2005 | PMID: 15642173 |
Histopathological characteristics of BRCA1- and BRCA2-associated intraperitoneal cancer: a clinic-based study. | Piek JM | Familial cancer | 2003 | PMID: 14574155 |
Molecular evidence for putative tumour suppressor genes on chromosome 13q specific to BRCA1 related ovarian and fallopian tube cancer. | Jongsma AP | Molecular pathology : MP | 2002 | PMID: 12354934 |
Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families. | Verhoog LC | European journal of cancer (Oxford, England : 1990) | 2001 | PMID: 11597388 |
BRCA1 and BRCA2 mutation analysis in 86 early onset breast/ovarian cancer patients. | Garvin AM | Journal of medical genetics | 1997 | PMID: 9429140 |
Low proportion of BRCA1 and BRCA2 mutations in Finnish breast cancer families: evidence for additional susceptibility genes. | Vehmanen P | Human molecular genetics | 1997 | PMID: 9361038 |
A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. | Peelen T | American journal of human genetics | 1997 | PMID: 9150151 |
Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core. | Couch FJ | Human mutation | 1996 | PMID: 8807330 |
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Text-mined citations for rs80357636 ...
HelpRecord last updated Jul 15, 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.