ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9294C>G (p.Tyr3098Ter) (rs80359200)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031812 SCV000282471 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000045784 SCV000073797 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr3098*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80359200, ExAC 0.01%). This variant has been reported in individuals with breast and/or ovarian cancer (PMID: 12698193, 24728189, 26787237), prostate cancer (PMID: 23569316), and pancreatic cancer (PMID: 26845104). This variant is also known as 9522C>G in the literature. ClinVar contains an entry for this variant (Variation ID: 38229). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000074562 SCV000108647 pathogenic not provided 2018-09-04 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.9294C>G at the cDNA level and p.Tyr3098Ter (Y3098X) at the protein level. The substitution, also denoted BRCA2 9522C>G using alternate nomenclature, creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in multiple individuals with a personal and/or family history of breast and/or ovarian cancer (Frank 1998, The Scottish/Northern Irish BRCA1/BRCA2 Consortium 2003, Lubinski 2004, Kurian 2008, Kwong 2016) and is considered pathogenic.
Ambry Genetics RCV000131041 SCV000185971 pathogenic Hereditary cancer-predisposing syndrome 2018-04-12 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
University of Washington Department of Laboratory Medicine, University of Washington RCV000210096 SCV000266052 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031812 SCV000296654 pathogenic Breast-ovarian cancer, familial 2 2015-06-16 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031812 SCV000328102 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031812 SCV000488714 pathogenic Breast-ovarian cancer, familial 2 2016-05-26 criteria provided, single submitter clinical testing
Baylor Genetics RCV000465472 SCV000540995 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045784 SCV000592274 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Color RCV000131041 SCV000684052 pathogenic Hereditary cancer-predisposing syndrome 2015-01-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045784 SCV000695234 pathogenic Hereditary breast and ovarian cancer syndrome 2017-03-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9294C>G (p.Tyr3098X) 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.9331G>T [p.Glu3111X], c.9382C>T [p.Arg3128X], and c.9403delC [p.Leu3135fsX28]). The variant lies within a nucleic acid-binding, OB-fold domain (InterPro) and 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 0.0000083 (1/120548 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Several publications cite the variant in patients and classify it as a pathogenic mutation (e.g., Kwong_BRCA_JMG_2015). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000031812 SCV000839911 pathogenic Breast-ovarian cancer, familial 2 2018-04-27 criteria provided, single submitter clinical testing A heterozygous c.9294C>G (p.Tyr3098*) pathogenic variant in the BRCA2 gene was detected in this individual. This variant has been previously described in multiple individuals with breast, ovarian, prostate and pancreatic cancer (PMID: 12698193, 24728189, 26787237, 23569316, 26845104).Therefore, we consider this variant to be pathogenic. [alaimo, 2018-01-30]
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000031812 SCV000883122 pathogenic Breast-ovarian cancer, familial 2 2018-11-21 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000074562 SCV000885085 pathogenic not provided 2018-01-25 criteria provided, single submitter clinical testing The BRCA2 c.9294C>G; p.Tyr3098Ter variant (rs80359200), also known as 9522C>G, is reported in the literature in individuals and families with hereditary breast and ovarian cancer syndrome (Lubinski 2004, Scottish/Northern Irish BRCA1/BRCA2 Consortium 2003), and is classified as pathogenic in ClinVar (Variation ID: 38229). This variant is found in the general population with a low overall allele frequency of 0.001% (3/276620 alleles) in the Genome Aggregation Database. This variant induces a premature termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-medicated decay. Based on available information, this variant is considered pathogenic. References: Lubinski J et al. Cancer variation associated with the position of the mutation in the BRCA2 gene. Fam Cancer. 2004;3(1):1-10. Scottish/Northern Irish BRCAI/BRCA2 Consortium. BRCA1 and BRCA2 mutations in Scotland and Northern Ireland. Br J Cancer. 2003;88(8):1256-62.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000074562 SCV000887959 pathogenic not provided 2015-06-16 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763331 SCV000894008 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3 2018-10-31 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031812 SCV000054420 pathogenic Breast-ovarian cancer, familial 2 2013-01-03 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031812 SCV000147604 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045784 SCV000587997 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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