ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.3149C>A (p.Thr1050Asn) (rs373040333)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129015 SCV000172914 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000129015 SCV000902807 likely benign Hereditary cancer-predisposing syndrome 2016-03-02 criteria provided, single submitter clinical testing
Counsyl RCV000662424 SCV000784875 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-01-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000197620 SCV000896648 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000213740 SCV000279357 uncertain significance not provided 2018-09-04 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.3149C>A at the cDNA level, p.Thr1050Asn (T1050N) at the protein level, and results in the change of a Threonine to an Asparagine (ACT>AAT). This variant has been reported in at least one individual with colon cancer and another with early onset breast cancer (Tung 2015, Pearlman 2017, Yurgelun 2017). BRIP1 Thr1050Asn was observed at an allele frequency of 0.08% (24/30,782) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is located in the BRCA1 binding domain (Cantor 2011). 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 BRIP1 Thr1050Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000197620 SCV000255168 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-06-25 criteria provided, single submitter clinical testing This sequence change replaces threonine with asparagine at codon 1050 of the BRIP1 protein (p.Thr1050Asn). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs373040333, ExAC 0.08%). This variant has been reported in two individuals affected with colorectal cancer (PMID: 27978560, 28135145), and two individuals affected with esophageal cancer (PMID: 21279724). ClinVar contains an entry for this variant (Variation ID: 140825). 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: "Deleterious"; PolyPhen-2: "Benign"; 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000213740 SCV000887999 uncertain significance not provided 2018-01-26 criteria provided, single submitter clinical testing

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