ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2344A>G (p.Ile782Val) (rs142806416)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131421 SCV000186402 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000409672 SCV000489973 uncertain significance Fanconi anemia, complementation group J 2016-08-30 criteria provided, single submitter clinical testing
Counsyl RCV000410875 SCV000489974 uncertain significance Neoplasm of ovary 2016-08-30 criteria provided, single submitter clinical testing
GeneDx RCV000759709 SCV000565723 uncertain significance not provided 2018-05-24 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2344A>G at the cDNA level, p.Ile782Val (I782V) at the protein level, and results in the change of an Isoleucine to a Valine (ATA>GTA). This variant has been reported in individuals with breast cancer and pancreatic cancer (Easton 2016, Shindo 2017). BRIP1 Ile782Val was not observed at a significant frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRIP1 Ile782Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000234751 SCV000291011 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 782 of the BRIP1 protein (p.Ile782Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs142806416, ExAC 0.006%). This variant has been reported in the literature in individuals affected with breast cancer and pancreatic cancer as well as in an unaffected individual (PMID: 26921362, 28767289). ClinVar contains an entry for this variant (Variation ID: 142346). 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 valine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Mendelics RCV000409672 SCV000839370 uncertain significance Fanconi anemia, complementation group J 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000483323 SCV000600904 uncertain significance not specified 2017-03-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759709 SCV000889214 uncertain significance not provided 2017-09-29 criteria provided, single submitter clinical testing

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