ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5496_5506delinsA (p.Val1833fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5496_5506delinsA (p.Val1833fs)
Variation ID: 55597 Accession: VCV000055597.10
- Type and length
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Indel, 11 bp
- Location
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Cytogenetic: 17q21.31 17: 43045764-43045774 (GRCh38) [ NCBI UCSC ] 17: 41197781-41197791 (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 May 1, 2024 Dec 15, 2017 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- V1786fs, V1833fs, V1854fs, V729fs
- Other names
- 5615del11insA
- Canonical SPDI
- NC_000017.11:43045763:CTCGGGTCACC: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
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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) |
reviewed by expert panel
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Dec 15, 2017 | RCV000112681.11 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 8, 2022 | RCV000582609.13 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 24, 2017 | RCV000657203.12 |
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
(Dec 15, 2017)
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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)
Study: ENIGMA
Accession: SCV000783569.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Mar 30, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000688639.2
First in ClinVar: Feb 19, 2018 Last updated: Jan 08, 2022 |
Comment:
This variant alters 11 nucleotides in exon 23 in the BRCA1 gene, causing a frameshift and disruption to the BRCT domain that is important for … (more)
This variant alters 11 nucleotides in exon 23 in the BRCA1 gene, causing a frameshift and disruption to the BRCT domain that is important for phosphopeptide binding and DNA damage response (PMID: 25701377). This variant has been observed in at least 15 individuals and families affected with breast and ovarian cancer (PMID: 16455195, 22798144) and an individual affected with melanoma (PMID: 23910109). This is a suspected founder mutation in Asia with many case reports from Korea (PMID: 21497495, 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is 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: SCV000326340.4
First in ClinVar: Apr 01, 2014 Last updated: Dec 11, 2022 |
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Pathogenic
(Sep 08, 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: SCV002651012.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.5496_5506del11insA pathogenic mutation, located in coding exon 22 of the BRCA1 gene, results from the deletion of 11 nucleotides and insertion of one nucleotide … (more)
The c.5496_5506del11insA pathogenic mutation, located in coding exon 22 of the BRCA1 gene, results from the deletion of 11 nucleotides and insertion of one nucleotide causing a translational frameshift with a predicted alternate stop codon (p.V1833Sfs*7). This alteration occurs at the 3' terminus of BRCA1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 31 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant has been reported in numerous HBOC individuals, notably among the Korean population (Kim SI et al. Cancer Res Treat, 2022 Jul; Ficarazzi F et al. Breast, 2021 Aug;58:121-129; Kim SI et al. Cancer Res Treat, 2020 Oct;52:1229-1241; Yi EJ et al. Ann Thorac Surg, 2013 Aug;96:677-80; Kang E et al. J Breast Cancer, 2013 Sep;16:245-53; Kim H et al. Breast Cancer Res Treat, 2012 Aug;134:1315-26; Ahn SH et al. Cancer Lett, 2007 Jan;245:90-5). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Nov 24, 2017)
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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: SCV000778929.1
First in ClinVar: Jul 09, 2018 Last updated: Jul 09, 2018 |
Comment:
This combined deletion and insertion is denoted BRCA1 c.5496_5506del11insA at the cDNA level and p.Val1833SerfsX7 (V1833SfsX7) at the protein level. The surrounding sequence is CTGT[del11][insA]AGTG. … (more)
This combined deletion and insertion is denoted BRCA1 c.5496_5506del11insA at the cDNA level and p.Val1833SerfsX7 (V1833SfsX7) at the protein level. The surrounding sequence is CTGT[del11][insA]AGTG. The variant causes a frameshift, which changes a Valine to a Serine at codon 1833, and creates a premature stop codon at position 7 of the new reading frame. Due to the position of the variant, nonsense mediated decay is not expected to occur, but the variant might cause loss of normal protein function through protein truncation. The disrupted region at the end of the gene includes a portion of the BRCT2 domain and a region known to interact with multiple proteins (Paul 2014, UniProt). BRCA1 c.5496_5506del11insA has been observed in multiple breast and/or ovarian cancer families and has been reported as a possible Korean founder variant (Ahn 2007, Seong 2009, Han 2011, Jang 2012, Kim 2012, Kim 2017). Based on currently available information, we consider this variant to be pathogenic. (less)
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Pathogenic
(Nov 24, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888949.2
First in ClinVar: Mar 13, 2019 Last updated: Jan 03, 2022 |
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Pathogenic
(Jul 19, 2006)
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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: SCV000145547.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Korean
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Korean
Geographic origin: Korean
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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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Effect of BRCA1/2 Mutational Status on Survival Outcomes According to Secondary Cytoreductive Surgery and Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer: A Real-World Evidence Study. | Kim SI | Cancer research and treatment | 2023 | PMID: 35879854 |
Towards population-based genetic screenings for breast and ovarian cancer: A comprehensive review from economic evaluations to patient perspectives. | Ficarazzi F | Breast (Edinburgh, Scotland) | 2021 | PMID: 34022715 |
Germline and Somatic BRCA1/2 Gene Mutational Status and Clinical Outcomes in Epithelial Peritoneal, Ovarian, and Fallopian Tube Cancer: Over a Decade of Experience in a Single Institution in Korea. | Kim SI | Cancer research and treatment | 2020 | PMID: 32718143 |
The korean hereditary breast cancer study: review and future perspectives. | Kang E | Journal of breast cancer | 2013 | PMID: 24155753 |
BRCA1 gene mutation in thymic malignant melanoma. | Yi EJ | The Annals of thoracic surgery | 2013 | PMID: 23910109 |
Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. | Kim H | Breast cancer research and treatment | 2012 | PMID: 22798144 |
BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. | Ahn SH | Cancer letters | 2007 | PMID: 16455195 |
Text-mined citations for rs273902775 ...
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.