ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.7069_7070del (p.Leu2357fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.7069_7070del (p.Leu2357fs)
Variation ID: 38082 Accession: VCV000038082.77
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 13q13.1 13: 32354921-32354922 (GRCh38) [ NCBI UCSC ] 13: 32929058-32929059 (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 Apr 22, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.7069_7070del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Leu2357fs frameshift NM_000059.3:c.7069_7070delCT NC_000013.11:g.32354922_32354923del NC_000013.10:g.32929059_32929060del NG_012772.3:g.44443_44444del LRG_293:g.44443_44444del U43746.1:n.7297_7298delCT - Protein change
- Other names
- 2357delCT
- 7297_7298delCT
- 7297delCT
- Canonical SPDI
- NC_000013.11:32354920:TCT: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
Help
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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BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18935 | 19094 |
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 (18) |
reviewed by expert panel
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Apr 22, 2016 | RCV000031664.30 | |
Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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Jul 31, 2024 | RCV000045136.56 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 3, 2024 | RCV000131032.21 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jan 11, 2024 | RCV000195404.31 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 2, 2020 | RCV001310136.9 | |
Pathogenic (1) |
no assertion criteria provided
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- | RCV001353880.10 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 27, 2024 | RCV003473208.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 20, 2021 | RCV003149600.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 12, 2023 | RCV004541046.1 |
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
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, 2
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282439.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Jan 01, 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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Genologica Medica
Additional submitter:
Servicio Andaluz de Salud, Hospital Universitario Virgen de la Victoria
Accession: SCV000577969.1
First in ClinVar: Nov 05, 2016 Last updated: Nov 05, 2016 |
Family history: yes
Ethnicity/Population group: Causasians
Geographic origin: Spain
Tissue: Blood
Secondary finding: no
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Pathogenic
(Apr 24, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000271332.4
First in ClinVar: May 29, 2016 Last updated: Jul 06, 2020 |
Comment:
The p.Leu2357ValfsX2 variant in BRCA2 has been identified in >30 individuals with BRCA2-associated cancers (Garvin 1997, Spearman 2008, Borg 2010, Caux-Moncoutier 2011, Zhang 2011, Breast … (more)
The p.Leu2357ValfsX2 variant in BRCA2 has been identified in >30 individuals with BRCA2-associated cancers (Garvin 1997, Spearman 2008, Borg 2010, Caux-Moncoutier 2011, Zhang 2011, Breast Cancer Information Core (BIC) database). This variant has also been identified in 7/12892 European chromosomes by the Genome Aggregation Database (GnomAD, http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 2357 and leads to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in individuals with HBOC. In addition, this variant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000282439.1). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon the predicted impact to the protein. ACMG/AMP Criteria applied: PVS1, PS4, PM2. (less)
Number of individuals with the variant: 21
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Pathogenic
(Jul 01, 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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Department of Medical Genetics, Oslo University Hospital
Accession: SCV000605676.3
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
Number of individuals with the variant: 3
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Pathogenic
(Jul 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV000838849.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(May 08, 2023)
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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: SCV000296725.7
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. The frequency of this … (more)
This frameshift variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. The frequency of this variant in the general population, 0.000054 (7/128928 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with breast cancer (PMID: 9429140 (1997)), ovarian cancer (PMID: 29084914 (2018), 30322717 (2018), 31263571 (2019)), colorectal cancer (PMID: 27978560 (2016)), and pancreatic cancer (PMID: 31948886 (2020), 32853339 (2021)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 18, 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: SCV000185962.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.7069_7070delCT pathogenic mutation, located in coding exon 13 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 7069 to … (more)
The c.7069_7070delCT pathogenic mutation, located in coding exon 13 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 7069 to 7070, causing a translational frameshift with a predicted alternate stop codon (p.L2357Vfs*2). This mutation has been reported in multiple hereditary breast and ovarian cancer (HBOC) cohorts (Garvin AM et al. J. Med. Genet. 1997 Dec;34:990-5; Thomassen M et al. Acta Oncol. 2008;47:772-7; Borg A et al. Hum. Mutat. 2010 Mar;31:E1200-40; Zhang S et al. Gynecol. Oncol. 2011 May;121:353-7; Litton JK et al. Cancer. 2012 Jan;118:321-5; Chong HK et al. PLoS ONE, 2014 May;9:e97408; Song H et al. Hum Mol Genet, 2014 Sep;23:4703-9; Labidi-Galy SI et al. Clin. Cancer Res. 2018 Jan;24:326-333; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Bertelsen B et al. NPJ Genom Med, 2019 Jun;4:13). This mutation has also been reported in prostate and pancreatic cancer cohorts (Schwartz M et al. Clin Genet, 2019 12;96:579-584; Boyle JL et al. JCO Precis Oncol, 2020 Mar;4; Moses M et al. Oncotarget, 2020 Jan;11:15-21). Of note, this alteration is also designated as 7297delCT 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
(Sep 21, 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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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744510.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Aug 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Familial breast-ovarian cancer 2
Affected status: unknown
Allele origin:
germline
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Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434856.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
This c.7069_7070delCT (p.Leu2357Valfs*2) frameshift variant in the BRCA2 gene is predicted to introduce a premature translation termination codon. It has been reported in multiple unrelated … (more)
This c.7069_7070delCT (p.Leu2357Valfs*2) frameshift variant in the BRCA2 gene is predicted to introduce a premature translation termination codon. It has been reported in multiple unrelated patients and families affected with breast cancer [PMID 9429140, 18465347, 21120943, 21324516, 24504028] and is extremely rare in general population. Therefore, this variant in the BRCA2 gene is classified as pathogenic. (less)
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Pathogenic
(Feb 04, 2016)
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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: SCV000488257.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Apr 01, 2022)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226621.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP5, PM2, PVS1
Number of individuals with the variant: 2
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Pathogenic
(Nov 29, 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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Revvity Omics, Revvity
Accession: SCV003816123.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Jun 19, 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: SCV001160239.3
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
Comment:
The BRCA2 c.7069_7070del; p.Leu2357ValfsTer2 variant (rs80359636), also known as 7297delCT, has been reported in multiple individuals with early onset breast or ovarian cancer (Caux-Moncoutier 2011, … (more)
The BRCA2 c.7069_7070del; p.Leu2357ValfsTer2 variant (rs80359636), also known as 7297delCT, has been reported in multiple individuals with early onset breast or ovarian cancer (Caux-Moncoutier 2011, Cunningham 2014, Garvin 1997, Zhang 2011). It is listed as pathogenic in ClinVar (Variation ID: 38082) and is observed 7 times in the Genome Aggregation Database (7/276,822 alleles). This variant causes a frameshift by deleting two nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, the variant is considered to be pathogenic. References: Caux-Moncoutier V et al. EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients. Hum Mutat. 2011; 32(3):325-34. PMID: 21120943. Cunningham J et al. Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. Sci Rep. 2014; 4:4026. PMID: 24504028. Garvin A et al. BRCA1 and BRCA2 mutation analysis in 86 early onset breast/ovarian cancer patients. J Med Genet. 1997; 34(12):990-5. PMID: 9429140. Zhang S et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011; 121(2):353-7. PMID: 21324516. (less)
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Pathogenic
(Mar 01, 2024)
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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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Baylor Genetics
Accession: SCV005049484.1
First in ClinVar: Jun 09, 2024 Last updated: Jun 09, 2024 |
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Pathogenic
(Feb 09, 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: SCV004211885.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
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Pathogenic
(Nov 03, 2014)
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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
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000196001.1
First in ClinVar: Mar 29, 2015 Last updated: Mar 29, 2015 |
Tissue: Blood
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Pathogenic
(Aug 07, 2017)
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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
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695036.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The BRCA2 c.7069_7070delCT (p.Leu2357Valfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense … (more)
Variant summary: The BRCA2 c.7069_7070delCT (p.Leu2357Valfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 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 (e.g., c.7133C>G [p.Ser2378X], c.7180A>T [p.Arg2394X], and c.7360delA [p.Ile2454fs). One in silico tool predicts a damaging outcome for this variant. This variant was found in the large control database ExAC at a frequency of 0.000033 (4/121100 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been identified in numerous patients in published reports (e.g., Thomassen_Acta Oncol_2008). In addition, 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
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001448153.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Ovarian neoplasm (present)
Sex: female
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Pathogenic
(Jun 11, 2017)
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criteria provided, single submitter
Method: provider interpretation, clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: no
Allele origin:
maternal
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Geisinger Autism and Developmental Medicine Institute, Geisinger Health System
Accession: SCV000804428.2
First in ClinVar: Apr 09, 2018 Last updated: Dec 11, 2022 |
Comment:
This 6 year old male with global developmental delays (at-risk for mild intellectual disability), ADHD, disruptive behavior, and mild overgrowth was found to carry a … (more)
This 6 year old male with global developmental delays (at-risk for mild intellectual disability), ADHD, disruptive behavior, and mild overgrowth was found to carry a maternally inherited 2 bp deletion in the BRCA2 gene. The c.7069_7070delCT pathogenic variant in the BRCA2 gene, previously reported as 7297delCT using alternate nomenclature, has been published in association with early-onset breast cancer, ovarian cancer, and prostate cancer (Garvin et al., 1997; Zhang et al., 2011; Cunningham et al., 2014; Song et al., 2014; Ellingson et al., 2015; Decker et al., 2016). The deletion causes a frameshift and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Given that this is an adult-onset condition, the patient is not expected to be affected at this time. The patient's mother has not been formally evaluated in the oncology setting, so her current status is unknown. (less)
Observation 1:
Clinical Features:
Global developmental delay (present) , Attention deficit hyperactivity disorder (present) , Behavioral abnormality (present) , Overgrowth (present)
Age: 0-9 years
Sex: male
Secondary finding: yes
Testing laboratory: GeneDx
Date variant was reported to submitter: 2017-05-20
Testing laboratory interpretation: Pathogenic
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Global developmental delay (present) , Attention deficit hyperactivity disorder (present) , Behavioral abnormality (present) , Overgrowth (present)
Age: 0-9 years
Sex: male
Testing laboratory: GeneDx
Date variant was reported to submitter: 2017-05-20
Testing laboratory interpretation: Pathogenic
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Pathogenic
(Mar 04, 2020)
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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: SCV000210786.15
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
Observed in multiple individuals with BRCA2-related cancers (Garvin 1997, Zhang 2011, Cunningham 2014, Song 2014, Ellingson 2015, Decker 2016, Afghahi 2017); Frameshift variant predicted to … (more)
Observed in multiple individuals with BRCA2-related cancers (Garvin 1997, Zhang 2011, Cunningham 2014, Song 2014, Ellingson 2015, Decker 2016, Afghahi 2017); 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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26745875, 24728189, 26681312, 26296701, 29084914, 9429140, 21324516, 24830819, 20104584, 21120943, 27087322, 24504028, 28166811, 28087643, 27978560, 29339979, 30720243, 30322717, 31432501, 31447099, 31263571, 31948886, 32853339, 30787465, 33087929) (less)
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Pathogenic
(Oct 20, 2021)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003838832.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Oct 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004100706.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
Comment:
Criteria applied: PVS1,PS4,PM5_STR
Clinical Features:
Breast carcinoma (present)
Sex: female
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Pathogenic
(Jan 03, 2024)
|
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: SCV000292173.5
First in ClinVar: Jul 08, 2016 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 2 nucleotides in exon 14 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known … (more)
This variant deletes 2 nucleotides in exon 14 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 7297delCT in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over ten individuals affected with breast and/or ovarian cancer (PMID: 9667259, 16234499, 18824701, 20104584, 21324516, 21913181, 24504028, 24549055, 24728189), as well as colorectal cancer (PMID: 27978560) and high grade prostate cancer (PMID: 34700141). This variant has been identified in 7/282332 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 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
(Jan 11, 2024)
|
criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000073149.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Leu2357Valfs*2) in the BRCA2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Leu2357Valfs*2) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs756538291, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 9429140, 21324516, 24504028, 24728189). This variant is also known as 7297delCT. ClinVar contains an entry for this variant (Variation ID: 38082). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Dec 12, 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: SCV004762720.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The BRCA2 c.7069_7070delCT variant is predicted to result in a frameshift and premature protein termination (p.Leu2357Valfs*2). This variant has been reported to be causative for … (more)
The BRCA2 c.7069_7070delCT variant is predicted to result in a frameshift and premature protein termination (p.Leu2357Valfs*2). This variant has been reported to be causative for hereditary cancer such as breast, ovarian, or colorectal cancers (reported as 7297delCT in Garvin et al. 1997. PubMed ID: 9429140; eTable 3, Pearlman et al. 2017. PubMed ID: 27978560; Table S3, Labidi-Galy et al. 2018. PubMed ID: 29084914; Heramb et al. 2018. PubMed ID: 29339979). This variant is reported in 0.0054% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/38082/). Frameshift variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Mar 27, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004812135.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
Criteria applied: PVS1,PM5_STR
Clinical Features:
Family history of cancer (present)
Sex: male
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Pathogenic
(Feb 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004844359.1
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 2 nucleotides in exon 14 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known … (more)
This variant deletes 2 nucleotides in exon 14 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 7297delCT in the literature according to the BIC nomenclature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over ten individuals affected with breast and/or ovarian cancer (PMID: 9667259, 16234499, 18824701, 20104584, 21324516, 21913181, 24504028, 24549055, 24728189), as well as colorectal cancer (PMID: 27978560) and high grade prostate cancer (PMID: 34700141). This variant has been identified in 7/282332 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 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: 5
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Pathogenic
(Jul 31, 2024)
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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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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002761181.4
First in ClinVar: Dec 17, 2022 Last updated: Aug 04, 2024 |
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Pathogenic
(Apr 02, 2020)
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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 Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499684.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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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, 2
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: SCV000327588.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Aug 10, 2020)
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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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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761530.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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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, 2
Affected status: yes
Allele origin:
germline
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Accession: SCV005045980.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
PVS1; PM5_PTC_Strong
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Pathogenic
(Jun 01, 2021)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001249490.24
First in ClinVar: May 12, 2020 Last updated: Aug 04, 2024 |
Number of individuals with the variant: 3
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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: SCV000587883.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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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 2
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147015.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 7
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Spain
Observation 4:
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian Non Hispanic
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: English, Scottish, French
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Welsh, English
Geographic origin: Canada
Observation 8:
Number of individuals with the variant: 16
Ethnicity/Population group: Western European
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Caucasian, Adopted
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Pathogenic
(Apr 23, 2013)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000054271.6
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2016 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
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: SCV000592097.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA2 p.Leu2357ValfsX2 variant was identified in 2 of 2856 proband chromosomes (frequency: 0.001) from individuals or families with Breast and/or Ovarian cancer (Garvin, 1997; … (more)
The BRCA2 p.Leu2357ValfsX2 variant was identified in 2 of 2856 proband chromosomes (frequency: 0.001) from individuals or families with Breast and/or Ovarian cancer (Garvin, 1997; Zhang, 2011). The variant was also identified in dbSNP (ID: rs80359636) “With pathogenic allele”, HGMD, LOVD, ClinVar database, the BIC database (31X with Important clinical importance), and UMD (34X as a class 5-causal variant). The variant was classified as a pathogenic variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). The p.Leu2357ValfsX2 deletion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 2357 and leads to a premature stop codon 2 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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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, 2
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: SCV000733293.1 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: SCV001905759.1 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, 2
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV004243752.1
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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Emergence of polyclonal BRCA2 reversions following PARP inhibitor treatment: An illustrative case report. | McFarland TR | Cancer treatment and research communications | 2021 | PMID: 34700141 |
Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer. | Darst BF | Journal of the National Cancer Institute | 2021 | PMID: 32853339 |
Exome sequencing and characterization of 49,960 individuals in the UK Biobank. | Van Hout CV | Nature | 2020 | PMID: 33087929 |
Pathogenic Germline DNA Repair Gene and HOXB13 Mutations in Men With Metastatic Prostate Cancer. | Boyle JL | JCO precision oncology | 2020 | PMID: 32923906 |
Evaluation of the genomic alterations in the androgen receptor gene during treatment with high-dose testosterone for metastatic castrate-resistant prostate cancer. | Moses M | Oncotarget | 2020 | PMID: 32002120 |
Rare Germline Pathogenic Mutations of DNA Repair Genes Are Most Strongly Associated with Grade Group 5 Prostate Cancer. | Wu Y | European urology oncology | 2020 | PMID: 31948886 |
Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: agibbs@bcm.edu | American journal of human genetics | 2019 | PMID: 31447099 |
Familial pancreatic adenocarcinoma: A retrospective analysis of germline genetic testing in a French multicentre cohort. | Schwartz M | Clinical genetics | 2019 | PMID: 31432501 |
High frequency of pathogenic germline variants within homologous recombination repair in patients with advanced cancer. | Bertelsen B | NPJ genomic medicine | 2019 | PMID: 31263571 |
Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer. | Labidi-Galy SI | Clinical cancer research : an official journal of the American Association for Cancer Research | 2018 | PMID: 29084914 |
Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer. | Pearlman R | JAMA oncology | 2017 | PMID: 27978560 |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
The validation and clinical implementation of BRCAplus: a comprehensive high-risk breast cancer diagnostic assay. | Chong HK | PloS one | 2014 | PMID: 24830819 |
The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. | Song H | Human molecular genetics | 2014 | PMID: 24728189 |
Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. | Castéra L | European journal of human genetics : EJHG | 2014 | PMID: 24549055 |
Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. | Cunningham JM | Scientific reports | 2014 | PMID: 24504028 |
Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. | Mavaddat N | Journal of the National Cancer Institute | 2013 | PMID: 23628597 |
Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO). | Lecarpentier J | Breast cancer research : BCR | 2012 | PMID: 22762150 |
Earlier age of onset of BRCA mutation-related cancers in subsequent generations. | Litton JK | Cancer | 2012 | PMID: 21913181 |
Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. | Zhang S | Gynecologic oncology | 2011 | PMID: 21324516 |
EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients. | Caux-Moncoutier V | Human mutation | 2011 | PMID: 21120943 |
Risk of breast cancer in male BRCA2 carriers. | Evans DG | Journal of medical genetics | 2010 | PMID: 20587410 |
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 |
Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations. | Agalliu I | Clinical cancer research : an official journal of the American Association for Cancer Research | 2009 | PMID: 19188187 |
Prevalence and characteristics of pancreatic cancer in families with BRCA1 and BRCA2 mutations. | Kim DH | Familial cancer | 2009 | PMID: 18855126 |
Clinically applicable models to characterize BRCA1 and BRCA2 variants of uncertain significance. | Spearman AD | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2008 | PMID: 18824701 |
BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer. | Thomassen M | Acta oncologica (Stockholm, Sweden) | 2008 | PMID: 18465347 |
Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. | Tai YC | Journal of the National Cancer Institute | 2007 | PMID: 18042939 |
Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. | Nanda R | JAMA | 2005 | PMID: 16234499 |
Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. | van Asperen CJ | Journal of medical genetics | 2005 | PMID: 16141007 |
Unique de novo mutation of BRCA2 in a woman with early onset breast cancer. | Robson M | Journal of medical genetics | 2002 | PMID: 11836363 |
Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. | Frank TS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 1998 | PMID: 9667259 |
BRCA1 and BRCA2 mutation analysis in 86 early onset breast/ovarian cancer patients. | Garvin AM | Journal of medical genetics | 1997 | PMID: 9429140 |
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Text-mined citations for rs80359636 ...
HelpRecord last updated Aug 25, 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.