ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2705T>C (p.Ile902Thr) (rs1060501781)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000465302 SCV000547384 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-10-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 902 of the BRIP1 protein (p.Ile902Thr). 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 been observed in an individual affected with pancreatic cancer (PMID: 28767289). ClinVar contains an entry for this variant (Variation ID: 407876). 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.
Integrated Genetics/Laboratory Corporation of America RCV000589053 SCV000699701 uncertain significance not provided 2017-04-27 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.2705T>C (p.Ile902Thr) variant involves the alteration of a non-conserved nucleotide and 2/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome. However, these predictions have yet to be functionally assessed. The variant of interest was not observed in the large, broad control population, ExAC, 0/121400 control chromosomes. A clinical diagnostic laboratory classifies the 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.
Color RCV000773139 SCV000906645 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-25 criteria provided, single submitter clinical testing

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