ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6293C>T (p.Ser2098Phe) (rs80358867)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044890 SCV000072903 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 2098 of the BRCA2 protein (p.Ser2098Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs80358867, ExAC 0.01%). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 23961350, 28477318). This variant is also known as 6521C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 52048). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000222689 SCV000277628 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000656797 SCV000321474 uncertain significance not provided 2018-10-31 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6293C>T at the cDNA level, p.Ser2098Phe (S2098F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCT>TTT). Using alternate nomenclature, this variant would be defined as BRCA2 6521C>T or 6749C>T. This variant has been observed in at least two individuals with a personal and/or family history of breast and/or ovarian cancer (Solano 2012, Gabald? Barrios 2017). BRCA2 Ser2098Phe was not observed at a significant allele frequency in large population cohorts (Lek 2016). BRCA2 Ser2098Phe is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Ser2098Phe is pathogenic or benign. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000656797 SCV000600689 uncertain significance not provided 2019-02-04 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000222689 SCV000679721 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Counsyl RCV000113560 SCV000785248 uncertain significance Breast-ovarian cancer, familial 2 2017-06-13 criteria provided, single submitter clinical testing
Color RCV000222689 SCV000903293 likely benign Hereditary cancer-predisposing syndrome 2017-03-06 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113560 SCV000146811 uncertain significance Breast-ovarian cancer, familial 2 2006-07-20 no assertion criteria provided clinical testing

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