ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.8878C>T (p.Gln2960Ter)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.8878C>T (p.Gln2960Ter)
Variation ID: 52694 Accession: VCV000052694.44
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32379440 (GRCh38) [ NCBI UCSC ] 13: 32953577 (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 Apr 22, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.8878C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Gln2960Ter nonsense NC_000013.11:g.32379440C>T NC_000013.10:g.32953577C>T NG_012772.3:g.68961C>T LRG_293:g.68961C>T LRG_293t1:c.8878C>T LRG_293p1:p.Gln2960Ter U43746.1:n.9106C>T - Protein change
- Q2960*
- Other names
- 9106C>T
- Canonical SPDI
- NC_000013.11:32379439:C: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
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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 (4) |
criteria provided, multiple submitters, no conflicts
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Nov 19, 2023 | RCV000045646.21 | |
Pathogenic (8) |
reviewed by expert panel
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Apr 22, 2016 | RCV000077455.18 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 17, 2022 | RCV000162940.19 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 13, 2020 | RCV000223154.16 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 2, 2020 | RCV001310187.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 20, 2023 | RCV003473426.1 |
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: SCV000282462.1
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
(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
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Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000196020.1
First in ClinVar: Sep 27, 2014 Last updated: Sep 27, 2014 |
Tissue: Blood
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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: SCV001499782.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(Sep 22, 2020)
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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: SCV000600828.2
First in ClinVar: Sep 28, 2017 Last updated: Jan 03, 2022 |
Comment:
This nonsense variant causes the premature termination of BRCA2 protein synthesis. It has been reported in hereditary breast and/or ovarian cancer in the published literature … (more)
This nonsense variant causes the premature termination of BRCA2 protein synthesis. It has been reported in hereditary breast and/or ovarian cancer in the published literature (PMIDs: 27425403 (2016), 26852130 (2016), 25863477 (2015), 24312913 (2013), 23165508 (2013), 18821011 (2009), 17224268 (2007), 16982466 (2006), 16764716 (2006), 14531499 (2003), 10449599 (1999), 28091860 (2017), 29161300 (2017), 29339979 (2018), 29446198 (2018), 30606148 (2019), and 30702160 (2019)). This variant has not been reported in large, multi-ethnic general populations. Therefore, the variant is classified as pathogenic. (less)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 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: SCV000327982.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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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: SCV000838887.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(Jan 15, 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: SCV000488176.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
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Pathogenic
(Oct 20, 2023)
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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: SCV004211829.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Nov 19, 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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Invitae
Accession: SCV000073659.10
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln2960*) 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.Gln2960*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 10449599, 14531499, 16764716, 18821011, 24312913, 25863477, 26852130). This variant is also known as 9106C>T. ClinVar contains an entry for this variant (Variation ID: 52694). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 05, 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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695185.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The BRCA2 c.8878C>T (p.Gln2960X) 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.8878C>T (p.Gln2960X) 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.8902_8913delinsTCCC, p.Thr2968fsX47; c.8904delC, p.Val2969fsX7; c.8930delA, p.Tyr2977fsX11; c.8961_8964delGAGT, p.Ser2988fsX12). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120540 control chromosomes. This variant was reported in multiple individuals affected with HBOC with clear segregation with the disease (Aretini, 2003; Santarosa, 1999; Miolo, 2006) The vaiant is suspected to be a founder mutation in Italian population (Miolo, 2006). 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
(Apr 17, 2019)
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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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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450053.1
First in ClinVar: Dec 11, 2020 Last updated: Dec 11, 2020 |
Number of individuals with the variant: 1
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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: SCV000605642.3
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
Number of individuals with the variant: 1
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Pathogenic
(Oct 13, 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: SCV000278883.11
First in ClinVar: May 29, 2016 Last updated: Mar 04, 2023 |
Comment:
Nonsense 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; Observed … (more)
Nonsense 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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Santarosa 1999, Fruscalzo 2006, Miolo 2006, Manoukian 2007, Barber 2013, Safra 2013); Not observed in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 9106C>T; This variant is associated with the following publications: (PMID: 29907814, 18821011, 23165508, 26733283, 24131973, 27528623, 26852130, 29161300, 30606148, 25525159, 16764716, 26360800, 25341009, 10449599, 25863477, 24312913, 14531499, 17224268, 16982466, 28263838, 28091860, 29339979, 29446198, 28176296, 30702160, 31825140, 30787465, 30613976) (less)
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Pathogenic
(Oct 17, 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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Color Diagnostics, LLC DBA Color Health
Accession: SCV000684004.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 22 of the BRCA2 gene, creating a premature translation stop signal. This variant is also known as 9106C>T … (more)
This variant changes 1 nucleotide in exon 22 of the BRCA2 gene, creating a premature translation stop signal. This variant is also known as 9106C>T in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in more than 10 individuals affected with breast or ovarian cancer (PMID: 16982466, 17224268, 23165508, 28091860, 30606148, 32438681, 33471991, 35281878) and has been identified in 38 families among the CIMBA participants (PMID: 29446198). This variant has not been identified 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
(Aug 02, 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: SCV000213427.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.Q2960* pathogenic mutation (also known as c.8878C>T), located in coding exon 21 of the BRCA2 gene, results from a C to T substitution at … (more)
The p.Q2960* pathogenic mutation (also known as c.8878C>T), located in coding exon 21 of the BRCA2 gene, results from a C to T substitution at nucleotide position 8878. This changes the amino acid from a glutamine to a stop codon within coding exon 21. This mutation has been identified in multiple families with hereditary breast and ovarian cancer syndrome (Santarosa M et al. Int. J. Cancer. 1999 Sep;83:5-9; Miolo G et al. BMC Cancer. 2006 Jun;6:156; Manoukian S et al. Eur. J. Cancer 2007 Feb;43:601-6; Papi L et al. Breast Cancer Res. Treat. 2009 Oct;117:497-504; Alemar B et al. Cancer Genet. 2016 Sep;209:417-422). 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
(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: SCV000147480.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Western European
Observation 3:
Number of individuals with the variant: 6
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 4:
Number of individuals with the variant: 2
Ethnicity/Population group: Western European
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Pathogenic
(Jan 08, 2007)
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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: SCV000109253.2
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
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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: SCV000587974.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Pathogenic
(Aug 26, 2022)
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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: SCV002588929.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
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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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Comprehensive Analysis of Somatic Reversion Mutations in Homologous Recombination Repair (HRR) Genes in A Large Cohort of Chinese Pan-cancer Patients. | Zong H | Journal of Cancer | 2022 | PMID: 35281878 |
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 |
Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome. | Santonocito C | Cancers | 2020 | PMID: 32438681 |
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 |
Prevalence of BRCA1 and BRCA2 pathogenic and likely pathogenic variants in non-selected ovarian carcinoma patients in Brazil. | Cotrim DP | BMC cancer | 2019 | PMID: 30606148 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
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 |
BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC) probands from Southern Brazil: Are international testing criteria appropriate for this specific population? | Alemar B | PloS one | 2017 | PMID: 29161300 |
Retesting BRCA1/BRCA2 mutation negative male breast cancer patients using next generation sequencing technologies. | Rizzolo P | Breast cancer research and treatment | 2017 | PMID: 28091860 |
Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. | Alemar B | Cancer genetics | 2016 | PMID: 27425403 |
Tracking of the origin of recurrent mutations of the BRCA1 and BRCA2 genes in the North-East of Italy and improved mutation analysis strategy. | Cini G | BMC medical genetics | 2016 | PMID: 26852130 |
The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study. | Kang E | Breast cancer research and treatment | 2015 | PMID: 25863477 |
A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer. | Karami F | BioMed research international | 2013 | PMID: 24312913 |
Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor. | Barber LJ | The Journal of pathology | 2013 | PMID: 23165508 |
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 |
Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy. | Papi L | Breast cancer research and treatment | 2009 | PMID: 18821011 |
Germline mutations of TP53 and BRCA2 genes in breast cancer/sarcoma families. | Manoukian S | European journal of cancer (Oxford, England : 1990) | 2007 | PMID: 17224268 |
Four primary malignancies successively occurred in a BRCA2 mutation carrier: a case report. | Fruscalzo A | Cancer investigation | 2006 | PMID: 16982466 |
Phenotypic features and genetic characterization of male breast cancer families: identification of two recurrent BRCA2 mutations in north-east of Italy. | Miolo G | BMC cancer | 2006 | PMID: 16764716 |
Different expressivity of BRCA1 and BRCA2: analysis of 179 Italian pedigrees with identified mutation. | Aretini P | Breast cancer research and treatment | 2003 | PMID: 14531499 |
BRCA1 and BRCA2 genes: role in hereditary breast and ovarian cancer in Italy. | Santarosa M | International journal of cancer | 1999 | PMID: 10449599 |
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Text-mined citations for rs80359140 ...
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.