ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.9052_9057del (p.3015KS[2])
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.
Uncertain significance(12); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.9052_9057del (p.3015KS[2])
Variation ID: 185294 Accession: VCV000185294.36
- Type and length
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Deletion, 6 bp
- Location
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Cytogenetic: 13q13.1 13: 32379844-32379849 (GRCh38) [ NCBI UCSC ] 13: 32953981-32953986 (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 6, 2017 Sep 16, 2024 Jul 19, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.9052_9057del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.3015KS[2] inframe deletion NM_000059.4:c.9052_9057delAGTAAA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000059.3:c.9052_9057delAGTAAA NC_000013.11:g.32379848_32379853del NC_000013.10:g.32953985_32953990del NG_012772.3:g.69369_69374del LRG_293:g.69369_69374del - Protein change
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- Other names
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- Canonical SPDI
- NC_000013.11:32379843:TAAAAGTAAA:TAAA
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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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- Links
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
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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BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18962 | 19121 |
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
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
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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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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Nov 2, 2023 | RCV000164689.22 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Jul 19, 2024 | RCV000235417.24 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 16, 2015 | RCV000410153.10 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jun 17, 2024 | RCV000548721.18 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 8, 2021 | RCV002505207.8 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 17, 2023 | RCV004528911.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 24, 2024 | RCV001800486.12 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 2, 2024 | RCV004567250.1 |
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
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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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Uncertain significance
(Jan 02, 2024)
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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: SCV005059122.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
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Uncertain significance
(Dec 16, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000488041.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Uncertain significance
(Oct 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Medulloblastoma Familial prostate cancer Wilms tumor 1 Fanconi anemia complementation group D1 Breast-ovarian cancer, familial, susceptibility to, 2 Glioma susceptibility 3 Pancreatic cancer, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002814911.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Jan 11, 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: SCV000887953.5
First in ClinVar: Dec 19, 2017 Last updated: Jan 06, 2024 |
Comment:
In the published literature, the variant was identified in an individual affected with sporadic breast cancer (PMID: 21918853 (2012)) and in a family suspected of … (more)
In the published literature, the variant was identified in an individual affected with sporadic breast cancer (PMID: 21918853 (2012)) and in a family suspected of having hereditary breast/ovarian cancer (PMID: 29061375 (2018)). The variant was also reported in an individual with osteosarcoma (PMID: 26580448 (2015)). The frequency of this variant in the general population, 0.00032 (8/24908 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
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Uncertain significance
(Nov 02, 2023)
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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: SCV000684020.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant results in an in-frame deletion of two amino acids in the BRCA2 protein. This variant is also known as 9280_9285del and p.3014_3015delSK in … (more)
This variant results in an in-frame deletion of two amino acids in the BRCA2 protein. This variant is also known as 9280_9285del and p.3014_3015delSK in the literature. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individuals affected with a personal or family history of breast cancer (PMID: 21918853, 35753294). This variant has been identified in 10/281852 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Dec 25, 2023)
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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: SCV000635714.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This variant, c.9052_9057del, results in the deletion of 2 amino acid(s) of the BRCA2 protein (p.Lys3019_Ser3020del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.9052_9057del, results in the deletion of 2 amino acid(s) of the BRCA2 protein (p.Lys3019_Ser3020del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs763756705, gnomAD 0.03%). This variant has been observed in individual(s) with BRCA2-related cancers (PMID: 21918853, 26580448). This variant is also known as c.9280_9285del (p.3014_3015delSK) or S3018_K3019del. ClinVar contains an entry for this variant (Variation ID: 185294). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Likely benign
(Sep 03, 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: SCV000215356.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Uncertain significance
(Jul 19, 2024)
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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: SCV000292529.15
First in ClinVar: Jul 24, 2016 Last updated: Sep 16, 2024 |
Comment:
Observed in individuals with a personal and/or family history of BRCA2-related cancers and in a pediatric patient with osteosarcoma (PMID: 21918853, 26580448, 29061375, 38069422); In … (more)
Observed in individuals with a personal and/or family history of BRCA2-related cancers and in a pediatric patient with osteosarcoma (PMID: 21918853, 26580448, 29061375, 38069422); In silico analysis supports a deleterious effect on protein structure/function; In-framed deletion of 2 amino acids in a repetitive region; Also known as 9280_9285delAGTAAA; This variant is associated with the following publications: (PMID: 26580448, 21918853, 28243543, 31131967, 29061375, 31853058, 38069422, 12228710, 37216690) (less)
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Uncertain significance
(Jun 17, 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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Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV005205763.1
First in ClinVar: Sep 16, 2024 Last updated: Sep 16, 2024 |
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Uncertain significance
(Feb 05, 2022)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002532000.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA2 c.9052_9057delAGTAAA (p.K3019_S3020del) variant has been reported in at least three individuals with breast cancer (PMID: 21918853), suspected hereditary breast and/or ovarian cancer (PMID: … (more)
The BRCA2 c.9052_9057delAGTAAA (p.K3019_S3020del) variant has been reported in at least three individuals with breast cancer (PMID: 21918853), suspected hereditary breast and/or ovarian cancer (PMID: 29061375), and pediatric osteosarcoma (PMID: 26580448). It is also described as c.9280_9285del (p.3014_3015delSK) and (p. S3018_K3019del). The variant was observed in 8/24908 chromosomes of the African/African American subpopulation in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654) and has been reported in ClinVar (Variation ID 185294). The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (less)
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Uncertain significance
(May 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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BRCA2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004107341.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The BRCA2 c.9052_9057del6 variant is predicted to result in an in-frame deletion (p.Lys3019_Ser3020del). This variant is also known as c.9280_9285del (p.3014_3015delSK), has been reported in … (more)
The BRCA2 c.9052_9057del6 variant is predicted to result in an in-frame deletion (p.Lys3019_Ser3020del). This variant is also known as c.9280_9285del (p.3014_3015delSK), has been reported in individuals with breast and/or ovarian cancer (de Juan Jiménez et al. 2012. PubMed ID: 21918853; Capone et al. 2017. PubMed ID: 29061375. Table S1). This variant is reported in 0.032% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-32953980-CTAAAAG-C). In ClinVar, this variant has conflicting interpretations of likely benign and uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/185294/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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Uncertain significance
(Apr 17, 2023)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002049655.2
First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024 |
Comment:
The BRCA2 c.9052_9057del; p.Lys3019_Ser3020del variant (rs786202063), also published as c.9280_9285del; p.3014_3015delSK, is reported in the literature in an individual affected with breast cancer, although its … (more)
The BRCA2 c.9052_9057del; p.Lys3019_Ser3020del variant (rs786202063), also published as c.9280_9285del; p.3014_3015delSK, is reported in the literature in an individual affected with breast cancer, although its clinical significance was uncertain (de Juan Jimenez 2012). This variant is also reported in ClinVar (Variation ID: 185294). It is found on ten chromosomes (10/281852 alleles) in the Genome Aggregation Database. This variant deletes two amino acids, leaving the rest of the protein in-frame. Due to limited information, the clinical significance of the p.Lys3019_Ser3020del variant is uncertain at this time. References: de Juan Jimenez I et al. Low prevalence of BRCA1 and BRCA2 mutations in the sporadic breast cancer of Spanish population. Fam Cancer. 2012 Mar;11(1):49-56. PMID: 21918853. (less)
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Uncertain significance
(Mar 24, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003844242.3
First in ClinVar: Mar 26, 2023 Last updated: Jun 29, 2024 |
Comment:
Variant summary: BRCA2 c.9052_9057delAGTAAA (p.Lys3019_Ser3020del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant allele … (more)
Variant summary: BRCA2 c.9052_9057delAGTAAA (p.Lys3019_Ser3020del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant allele was found at a frequency of 2.8e-05 in 250472 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9052_9057delAGTAAA has been reported in the literature in individuals affected with breast cancer (e.g., deJuanJimenez_2021), individuals with a personal or family history of BRCA-related cancer (e.g., Houdayer_2012, Bisgin_2022, Capone_2018), and in a pediatric osteosarcoma case (e.g., Zhang_2015), however without strong evidence for causality. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Additionally, 4/4 computational tools predict no significant impact on normal splicing, and these predictions are supported by a functional study that found the variant had no effect on splicing at the cDNA level (e.g., Houdayer_2012). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 35753294, 29061375, 22505045, 28243543, 26580448, 21918853). ClinVar contains an entry for this variant (Variation ID: 185294). Based on the evidence outlined above, the variant was classified as uncertain significance. (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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Germline landscape of BRCAs by 7-site collaborations as a BRCA consortium in Turkey. | Bisgin A | Breast (Edinburgh, Scotland) | 2022 | PMID: 35753294 |
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. | Parsons MT | Human mutation | 2019 | PMID: 31131967 |
Evaluation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Mutation Detection. | Capone GL | The Journal of molecular diagnostics : JMD | 2018 | PMID: 29061375 |
Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment. | Vysotskaia VS | PeerJ | 2017 | PMID: 28243543 |
Germline Mutations in Predisposition Genes in Pediatric Cancer. | Zhang J | The New England journal of medicine | 2015 | PMID: 26580448 |
Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. | Houdayer C | Human mutation | 2012 | PMID: 22505045 |
Low prevalence of BRCA1 and BRCA2 mutations in the sporadic breast cancer of Spanish population. | de Juan Jiménez I | Familial cancer | 2012 | PMID: 21918853 |
Text-mined citations for rs786202063 ...
HelpRecord last updated Oct 27, 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.