ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1796_1800del (p.Thr598_Ser599insTer) (rs276174813)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129987 SCV000184811 pathogenic Hereditary cancer-predisposing syndrome 2017-07-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Breast Cancer Information Core (BIC) (BRCA2) RCV000031337 SCV000145940 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129987 SCV000683449 pathogenic Hereditary cancer-predisposing syndrome 2017-01-23 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031337 SCV000326611 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031337 SCV000677720 pathogenic Breast-ovarian cancer, familial 2 2017-03-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000168232 SCV000591768 pathogenic Hereditary breast and ovarian cancer syndrome 2015-04-08 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031337 SCV000282361 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000043887 SCV000210716 pathogenic not provided 2018-11-19 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.1796_1800delCTTAT at the cDNA level and p.Ser599Ter (S599X) at the protein level. The normal sequence with the bases that are deleted in brackets is ACAT[delCTTAT]AAAG. The substitution creates a nonsense variant, changing a Serine 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. This variant, also denoted 2024del5 using alternate nomenclature, has been reported in association with breast cancer, often in individuals of Greek descent (Ladopoulou 2002, Bayraktar 2012, Koumpis 2011). We consider this variant to be pathogenic.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000031337 SCV000839921 pathogenic Breast-ovarian cancer, familial 2 2017-05-25 criteria provided, single submitter clinical testing The c.1796_1800del (p.Ser599*) variant in the BRCA2 gene has been detected multiple patients with breast cancer [reported as 2022del5 in PMID 8988179]. This variant creates a premature stop codon at amino acid position 599 of the BRCA2 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant thus classified as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000168232 SCV000694563 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-10 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1796_1800delCTTAT (p.Ser599Terfs) 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. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications. In addition, multiple clinical diagnostic laboratories/databases cite the variant as "pathogenic." Therefore, the variant of interest has been classified as "Pathogenic."
Invitae RCV000168232 SCV000071900 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser599*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast cancer (PMID: 22009639, 8988179, 24549055, 22085629, 22798144). This variant is also known as c.1796delCTTAT and 2024del5 in the literature. ClinVar contains an entry for this variant (Variation ID: 37756). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031337 SCV000296660 pathogenic Breast-ovarian cancer, familial 2 2015-11-11 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000043887 SCV000887761 pathogenic not provided 2015-11-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031337 SCV000053942 pathogenic Breast-ovarian cancer, familial 2 2011-05-02 no assertion criteria provided clinical testing

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