Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.36dup (p.Glu13Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Sep 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.36dup (p.Glu13Ter)
Variation ID: 51509 Accession: VCV000051509.22
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32316490-32316491 (GRCh38) [ NCBI UCSC ] 13: 32890627-32890628 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 May 1, 2024 Sep 8, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000059.4:c.36dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Glu13Ter nonsense NM_000059.3:c.36dupT NC_000013.11:g.32316496dup NC_000013.10:g.32890633dup NG_012772.3:g.6017dup NG_017006.2:g.3873dup LRG_293:g.6017dup LRG_293t1:c.36dup U43746.1:n.264_265insT - Protein change
- E13*
- Other names
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264insT
- Canonical SPDI
- NC_000013.11:32316490:TTTTTT:TTTTTTT
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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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- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 |
18969 | 19128 | |
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. |
|---|---|---|---|---|
| Pathogenic (4) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000082917.15 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 26, 2024 | RCV000496400.18 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jul 3, 2020 | RCV000486380.10 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 31, 2023 | RCV001182330.14 | |
| Pathogenic (1) |
criteria provided, single submitter
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Aug 21, 2019 | RCV001798232.10 |
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
(Sep 08, 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
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000300286.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Apr 22, 2015)
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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: SCV000566348.3
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
This duplication of one nucleotide is denoted BRCA2 c.36dupT at the cDNA level and p.Glu13Ter (E13X) at the protein level. The normal sequence, with the … (more)
This duplication of one nucleotide is denoted BRCA2 c.36dupT at the cDNA level and p.Glu13Ter (E13X) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ATTTTT[T]GAAA. The duplication creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.36dupT, previously reported as 264dupT and 265insT using alternate nomenclature, has been observed in at least one family with hereditary breast cancer (Vaziri 2001). This variant is considered pathogenic. (less)
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Pathogenic
(Jul 03, 2020)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469421.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
Comment:
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in … (more)
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity. (less)
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Pathogenic
(Oct 05, 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: SCV001584649.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu13*) 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.Glu13*) 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 (rs80359393, gnomAD 0.06%). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 11139249, 29446198). This variant is also known as c.265insT. ClinVar contains an entry for this variant (Variation ID: 51509). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 07, 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: SCV002621307.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.36dupT pathogenic mutation, located in coding exon 1 of the BRCA2 gene, results from a duplication of T at nucleotide position 36, causing a … (more)
The c.36dupT pathogenic mutation, located in coding exon 1 of the BRCA2 gene, results from a duplication of T at nucleotide position 36, causing a translational frameshift with a predicted alternate stop codon (p.E13*). This pathogenic variant (referred to as 265insT) has been reported in one family with a strong history of breast cancer (Vaziri SA et al. Hum. Mutat. 2001;17:74). 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
(Apr 20, 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
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Department of Pathology and Molecular Medicine, Queen's University
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000588065.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
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Pathogenic
(Aug 21, 2019)
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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: SCV002043005.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
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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: SCV000326897.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Jul 31, 2023)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001347760.3
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant duplicates 1 nucleotide in exon 2 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant duplicates 1 nucleotide in exon 2 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is also known as 265insT in the literature. This variant has been reported in individuals with a personal or family history of breast and/or ovarian cancer (PMID: 11139249, 28692638, 29446198, 33471991). This variant has been identified in 1/31408 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
(Feb 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004813723.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
Variant summary: BRCA2 c.36dupT (p.Glu13X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is … (more)
Variant summary: BRCA2 c.36dupT (p.Glu13X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanismss for disease. The variant was absent in 251372 control chromosomes. c.36dupT has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Gao_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31825140). ClinVar contains an entry for this variant (Variation ID: 51509). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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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
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587528.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
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Pathogenic
(-)
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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: SCV000146041.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
|
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Pathogenic
(Jul 15, 2008)
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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: SCV000114991.2
First in ClinVar: Feb 09, 2014 Last updated: Sep 27, 2014 |
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Comment:
Comment:
This duplication of one nucleotide is denoted BRCA2 c.36dupT at the cDNA level and p.Glu13Ter (E13X) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ATTTTT[T]GAAA. The duplication creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.36dupT, previously reported as 264dupT and 265insT using alternate nomenclature, has been observed in at least one family with hereditary breast cancer (Vaziri 2001). This variant is considered pathogenic.
Comment:
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity.
Comment:
This sequence change creates a premature translational stop signal (p.Glu13*) 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 (rs80359393, gnomAD 0.06%). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 11139249, 29446198). This variant is also known as c.265insT. ClinVar contains an entry for this variant (Variation ID: 51509). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.36dupT pathogenic mutation, located in coding exon 1 of the BRCA2 gene, results from a duplication of T at nucleotide position 36, causing a translational frameshift with a predicted alternate stop codon (p.E13*). This pathogenic variant (referred to as 265insT) has been reported in one family with a strong history of breast cancer (Vaziri SA et al. Hum. Mutat. 2001;17:74). 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.
Comment:
This variant duplicates 1 nucleotide in exon 2 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is also known as 265insT in the literature. This variant has been reported in individuals with a personal or family history of breast and/or ovarian cancer (PMID: 11139249, 28692638, 29446198, 33471991). This variant has been identified in 1/31408 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.
Comment:
Variant summary: BRCA2 c.36dupT (p.Glu13X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanismss for disease. The variant was absent in 251372 control chromosomes. c.36dupT has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Gao_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31825140). ClinVar contains an entry for this variant (Variation ID: 51509). Based on the evidence outlined above, the variant was classified as pathogenic.
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. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
This duplication of one nucleotide is denoted BRCA2 c.36dupT at the cDNA level and p.Glu13Ter (E13X) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ATTTTT[T]GAAA. The duplication creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.36dupT, previously reported as 264dupT and 265insT using alternate nomenclature, has been observed in at least one family with hereditary breast cancer (Vaziri 2001). This variant is considered pathogenic.
Comment:
The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity.
Comment:
This sequence change creates a premature translational stop signal (p.Glu13*) 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 (rs80359393, gnomAD 0.06%). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 11139249, 29446198). This variant is also known as c.265insT. ClinVar contains an entry for this variant (Variation ID: 51509). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.36dupT pathogenic mutation, located in coding exon 1 of the BRCA2 gene, results from a duplication of T at nucleotide position 36, causing a translational frameshift with a predicted alternate stop codon (p.E13*). This pathogenic variant (referred to as 265insT) has been reported in one family with a strong history of breast cancer (Vaziri SA et al. Hum. Mutat. 2001;17:74). 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.
Comment:
This variant duplicates 1 nucleotide in exon 2 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is also known as 265insT in the literature. This variant has been reported in individuals with a personal or family history of breast and/or ovarian cancer (PMID: 11139249, 28692638, 29446198, 33471991). This variant has been identified in 1/31408 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.
Comment:
Variant summary: BRCA2 c.36dupT (p.Glu13X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanismss for disease. The variant was absent in 251372 control chromosomes. c.36dupT has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Gao_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31825140). ClinVar contains an entry for this variant (Variation ID: 51509). Based on the evidence outlined above, the variant was classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients. | Gao X | Human mutation | 2020 | PMID: 31825140 |
| Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| The First Nationwide Multicenter Prevalence Study of Germline BRCA1 and BRCA2 Mutations in Chinese Ovarian Cancer Patients. | Wu X | International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | 2017 | PMID: 28692638 |
| 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 |
| A novel de novo BRCA2 mutation of paternal origin identified in a Spanish woman with early onset bilateral breast cancer. | Diez O | Breast cancer research and treatment | 2010 | PMID: 19649703 |
| Frequency of BRCA1 and BRCA2 mutations in a clinic-based series of breast and ovarian cancer families. | Vaziri SA | Human mutation | 2001 | PMID: 11139249 |
Text-mined citations for rs80359393 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 10, 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.