ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2885T>C (p.Ile962Thr) (rs786201632)

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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 RCV000164008 SCV000214612 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence,in silico models in agreement (benign)
Invitae RCV000197368 SCV000255165 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-08-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 962 of the BRIP1 protein (p.Ile962Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). 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: 184706). 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 threonine 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.
Color RCV000164008 SCV000689360 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586686 SCV000699708 uncertain significance not provided 2016-09-02 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.2885T>C (p.Ile962Thr) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 120908 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Counsyl RCV000662667 SCV000785366 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-07-14 criteria provided, single submitter clinical testing

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