ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.69_79delGTGTCCCATCT (p.Cys24fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.69_79delGTGTCCCATCT (p.Cys24fs)
Variation ID: 55676 Accession: VCV000055676.30
- Type and length
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Deletion, 11 bp
- Location
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Cytogenetic: 17q21.31 17: 43124017-43124027 (GRCh38) [ NCBI UCSC ] 17: 41276034-41276044 (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 Apr 22, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.69_79delGTGTCCCATCT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Cys24fs frameshift NM_007294.4:c.70_80del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_007294.3:c.70_80delTGTCCCATCTG NM_007297.4:c.-18_-8del 5 prime UTR NM_007299.4:c.69_79delGTGTCCCATCT NP_009230.2:p.Cys24fs frameshift NM_007300.4:c.69_79delGTGTCCCATCT NP_009231.2:p.Cys24fs frameshift NR_027676.2:n.271_281delGTGTCCCATCT non-coding transcript variant NC_000017.11:g.43124018_43124028del NC_000017.10:g.41276035_41276045del NG_005905.2:g.93957_93967del LRG_292:g.93957_93967del U14680.1:n.189_199del11 - Protein change
- C24fs
- Other names
- 189del11
- 188del11
- 189_199delTGTCCCATCTG
- Canonical SPDI
- NC_000017.11:43124016:CAGATGGGACAC:C
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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
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 |
13037 | 14843 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jan 5, 2024 | RCV000049106.22 | |
Pathogenic (6) |
reviewed by expert panel
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Apr 22, 2016 | RCV000111682.20 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 19, 2022 | RCV000131391.18 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jul 18, 2023 | RCV000486060.18 |
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
(Apr 22, 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: SCV000282349.1
First in ClinVar: Mar 28, 2015 Last updated: Mar 28, 2015 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Apr 14, 2022)
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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: SCV001363982.2
First in ClinVar: Jun 22, 2020 Last updated: May 16, 2022 |
Comment:
Variant summary: BRCA1 c.70_80del11 (p.Cys24SerfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.70_80del11 (p.Cys24SerfsX13) 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 was absent in 251038 control chromosomes.The variant, c.70_80del11, has been reported in the literature in multiple individuals affected with breast and/or ovarian cancer (eg. Berman_1996, Hopper_1999, Alsop_2012, Dean_2015, Wong-Brown_2015). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine ClinVar submissions including one expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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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: SCV000326397.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Mar 04, 2019)
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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: SCV000186367.7
First in ClinVar: Aug 06, 2014 Last updated: Mar 04, 2023 |
Comment:
The c.70_80del11 pathogenic mutation, located in coding exon 1 of the BRCA1 gene, results from a deletion of 11 nucleotides at nucleotide positions 70 to … (more)
The c.70_80del11 pathogenic mutation, located in coding exon 1 of the BRCA1 gene, results from a deletion of 11 nucleotides at nucleotide positions 70 to 80, causing a translational frameshift with a predicted alternate stop codon (p.C24Sfs*13). This mutation has been reported in multiple individuals with hereditary breast, ovarian, and/or pancreatic cancer (Berman DB et al. Am. J. Hum. Genet. 1996 Jun;58:1166-76; Frank TS et al. J. Clin. Oncol. 2002 Mar;20:1480-90; Kurian A et al. J. Clin. Oncol. 2008 Oct;26(29):4752-8; Shindo K et al. J. Clin. Oncol. 2017 Oct;35(30):3382-3390). Of note, this alteration is also designated as 188del11 and 189del11 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)
Number of individuals with the variant: 1
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Pathogenic
(Mar 29, 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: SCV005058214.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
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Pathogenic
(Jan 21, 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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Genetic Services Laboratory, University of Chicago
Accession: SCV002065918.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
Comment:
DNA sequence analysis of the BRCA1 gene demonstrated a 11 base pair deletion in exon 2, c.70_80del. This pathogenic sequence change results in an amino … (more)
DNA sequence analysis of the BRCA1 gene demonstrated a 11 base pair deletion in exon 2, c.70_80del. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 12 amino acids downstream of the change, p.Cys24Serfs*13. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated BRCA1 protein with potentially abnormal function. The c.70_80del sequence change has not been described in the population databases such as ExAC and gnomAD (dbSNP rs1220450191). This pathogenic sequence change has previously been described in an individual with breast cancer and ovarian cancer (PMID: 7837387, 10498392, 25682074, 22711857, 26543556). (less)
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Pathogenic
(Mar 28, 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: SCV000677630.2
First in ClinVar: Mar 27, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(Jul 18, 2023)
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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: SCV000568440.6
First in ClinVar: Apr 27, 2017 Last updated: Jul 29, 2023 |
Comment:
Frameshift 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)
Frameshift 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 in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 189_199del11 or c.69_79delGTGTCCCATCT; This variant is associated with the following publications: (PMID: 16267036, 7837387, 7545954, 18779604, 26543556, 8651293, 12402332, 10498392, 8533757, 28767289, 31090900, 30787465, 31464824, 25682074, 36098958, 34022715, 34887416) (less)
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Pathogenic
(Jul 22, 2022)
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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: SCV000887731.4
First in ClinVar: Apr 27, 2017 Last updated: Jan 06, 2024 |
Comment:
This variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. It has not been reported … (more)
This variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, this variant has been reported in individuals with breast cancer, PMIDs: 22711857 (2012), 26543556 (2015), and 25682074 (2015)) and pancreatic cancer (PMID: 28767289 (2017)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 05, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000077119.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Cys24Serfs*13) 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.Cys24Serfs*13) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer and ovarian cancer (PMID: 2246425, 7837387, 10498392, 20104584, 22711857, 25682074, 26543556). This variant is also known as 188del11 and 189del11. ClinVar contains an entry for this variant (Variation ID: 55676). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 19, 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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Color Diagnostics, LLC DBA Color Health
Accession: SCV002052187.2
First in ClinVar: Jan 08, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant deletes the last 11 nucleotides in exon 2 in the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is … (more)
This variant deletes the last 11 nucleotides in exon 2 in 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. This variant is also known as 188del11 and 189del11 in the literature. This variant has been detected in over 10 individuals and families affected with breast and ovarian cancer (PMID: 7837387, 8651293, 10498392, 18779604, 22711857, 25682074, 26543556) and one individual each affected with endometrial (PMID: 8651293) and pancreatic cancer (PMID: 28767289). This variant has been identified in 21 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has not been identified 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
(Nov 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004823701.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This variant deletes the last 11 nucleotides in exon 2 in the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is … (more)
This variant deletes the last 11 nucleotides in exon 2 in 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. This variant is also known as 188del11 and 189del11 in the literature. This variant has been detected in over 10 individuals and families affected with breast and ovarian cancer (PMID: 7837387, 8651293, 10498392, 18779604, 22711857, 25682074, 26543556) and one individual each affected with endometrial (PMID: 8651293) and pancreatic cancer (PMID: 28767289). This variant has been identified in 21 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has not been identified 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)
Number of individuals with the variant: 1
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Pathogenic
(Feb 20, 2004)
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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: SCV000144182.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 11
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian Non Hispanic
Observation 3:
Number of individuals with the variant: 4
Ethnicity/Population group: Western European
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Native American
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587007.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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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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Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers. | Nones K | Annals of oncology : official journal of the European Society for Medical Oncology | 2019 | PMID: 31090900 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
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 |
Addressing health disparities in Hispanic breast cancer: accurate and inexpensive sequencing of BRCA1 and BRCA2. | Dean M | GigaScience | 2015 | PMID: 26543556 |
Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. | Wong-Brown MW | Breast cancer research and treatment | 2015 | PMID: 25682074 |
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 |
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 |
Performance of BRCA1/2 mutation prediction models in Asian Americans. | Kurian AW | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2008 | PMID: 18779604 |
Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. | Frank TS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2002 | PMID: 11896095 |
Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study. | Hopper JL | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 1999 | PMID: 10498392 |
The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. | Abeliovich D | American journal of human genetics | 1997 | PMID: 9042909 |
Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: a genetic study of 15 185delAG-mutation kindreds. | Berman DB | American journal of human genetics | 1996 | PMID: 8651293 |
A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening. | Shattuck-Eidens D | JAMA | 1995 | PMID: 7837387 |
A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. | Miki Y | Science (New York, N.Y.) | 1994 | PMID: 7545954 |
Postoperative respiratory failure due to acute eosinophilic pneumonia. | St John RC | Intensive care medicine | 1990 | PMID: 2246425 |
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Text-mined citations for rs80357696 ...
HelpRecord last updated Oct 13, 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.