ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2990C>T (p.Thr997Ile) (rs749978235)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000772635 SCV000905838 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-25 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000636087 SCV000896649 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780050 SCV000917070 uncertain significance not specified 2017-10-06 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.2990C>T (p.Thr997Ile) variant involves the alteration of a non-conserved nucleotide and 3/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome for this variant. However, these predictions have yet to be functionally assessed. This variant was found in 1/245770 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertian Significance (VUS)," until additional information becomes available.
Invitae RCV000636087 SCV000757519 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 997 of the BRIP1 protein (p.Thr997Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs749978235, ExAC 0.009%). This variant has not been reported in the literature in individuals with BRIP1-related disease. 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 isoleucine 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758995 SCV000887995 uncertain significance not provided 2018-07-03 criteria provided, single submitter clinical testing

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