ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.794-11T>C
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.794-11T>C
Variation ID: 52441 Accession: VCV000052441.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32332261 (GRCh38) [ NCBI UCSC ] 13: 32906398 (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 Aug 4, 2024 Jul 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.794-11T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000013.11:g.32332261T>C NC_000013.10:g.32906398T>C NG_012772.3:g.21782T>C LRG_293:g.21782T>C LRG_293t1:c.794-11T>C U43746.1:n.1022-11T>C - Protein change
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- Other names
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IVS9-11T>C
- Canonical SPDI
- NC_000013.11:32332260:T: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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Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00003
- 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
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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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
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (1) |
criteria provided, single submitter
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Jan 18, 2024 | RCV000045349.21 | |
Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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May 31, 2017 | RCV000112830.13 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jul 31, 2024 | RCV000504042.16 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 16, 2017 | RCV000580896.11 | |
Benign (4) |
criteria provided, single submitter
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Oct 23, 2020 | RCV001353607.17 |
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
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(Jun 15, 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: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743250.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
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Benign
(Jan 18, 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: SCV000073362.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
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Likely benign
(Jul 31, 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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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005090012.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024 |
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Benign
(Jun 25, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000730712.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Likely benign
(May 31, 2017)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
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: SCV000744393.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
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Likely benign
(May 03, 2017)
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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: SCV000785118.2
First in ClinVar: Jul 14, 2018 Last updated: Jul 14, 2018 |
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Benign
(Aug 06, 2021)
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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: SCV000917051.2
First in ClinVar: Jun 03, 2019 Last updated: Sep 08, 2021 |
Comment:
Variant summary: BRCA2 c.794-11T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly … (more)
Variant summary: BRCA2 c.794-11T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. This is supported by functional studies that have reported no impact on splicing (example, Houdayer_2012). The variant allele was found at a frequency of 2.9e-05 in 242116 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.794-11T>C has been reported in the literature as a VUS in settings of multigene panel testing of individuals affected with breast and/or colorectal cancer (example, Brandao_2011, Djursby_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Multiple co-occurrences with other pathogenic variant(s) have been reported in the UMD database and observed at our laboratory (UMD - BRCA1 c.2649insGGCA, p.Thr884AlafsX20; BRCA1 c.5106delA, p.Lys1702AsnfsX4; Our laboratory - BRCA1 c.5266dupC, p.Gln1756fsX74), providing supporting evidence for a benign role. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=2)/likely benign (n=4). Based on the evidence outlined above, the variant was classified as benign. (less)
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Benign
(Oct 23, 2020)
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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: SCV002048846.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Likely benign
(Mar 16, 2017)
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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: SCV000683918.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Uncertain significance
(Feb 20, 2004)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000145741.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Geographic origin: Western European
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
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Likely benign
(-)
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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: SCV000591714.2 First in ClinVar: Aug 28, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA2, EXON10, c.794-11T>C, variant was identified in at least one breast and/or ovarian cancer family from a cohort of 1800 unrelated probands (Brandao 2011). … (more)
The BRCA2, EXON10, c.794-11T>C, variant was identified in at least one breast and/or ovarian cancer family from a cohort of 1800 unrelated probands (Brandao 2011). The variant was also identified in the UMD (1X as an unclassified variant) and in the BIC database (3X with unknown clinical importance). The c.794-11T>C variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. One functional study using RT-PCR analysis demonstrated no effect of the variant on splicing (Brandao 2011). In addition, in silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, HumanSpliceFinder) does not predict a difference in splicing all four programs. Furthermore, this variant was identified by our laboratory in an individual with a co-occurring pathogenic mutation in BRCA1, increasing the likelihood that the c.794-11T>C variant does not have clinical importance. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign. (less)
Number of individuals with the variant: 2
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Likely benign
(-)
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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: SCV001906303.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
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Likely benign
(-)
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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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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954252.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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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New Pathogenic Germline Variants in Very Early Onset and Familial Colorectal Cancer Patients. | Djursby M | Frontiers in genetics | 2020 | PMID: 33193653 |
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 |
Characterisation of unclassified variants in the BRCA1/2 genes with a putative effect on splicing. | Brandão RD | Breast cancer research and treatment | 2011 | PMID: 21638052 |
The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Text-mined citations for rs81002822 ...
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.