ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.394A>T (p.Thr132Ser) (rs730881623)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000160320 SCV000217078 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000160320 SCV000911172 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-25 criteria provided, single submitter clinical testing
Counsyl RCV000662866 SCV000785755 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-11-20 criteria provided, single submitter clinical testing
GeneDx RCV000212300 SCV000210819 uncertain significance not provided 2018-08-24 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.394A>T at the cDNA level, p.Thr132Ser (T132S) at the protein level, and results in the change of a Threonine to a Serine (ACC>TCC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Thr132Ser was not observed at a significant frequency in large population cohorts (Lek 2016). Since Threonine and Serine share similar properties, this is considered a conservative amino acid substitution. BRIP1 Thr132Ser is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRIP1 Thr132Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000167936 SCV000218584 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-06-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 132 of the BRIP1 protein (p.Thr132Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs730881623, ExAC 0.009%). This variant has not been reported in the literature in individuals with a BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 182331). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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