ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.3730_3731del (p.Met1244fs) (rs730881646)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160359 SCV000210865 uncertain significance not provided 2015-09-06 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRIP1 is denoted c.3730_3731delAT at the cDNA level and p.Met1244ValfsX5 (M1244VfsX5) at the protein level. The normal sequence, with the bases that are deleted in braces, is AGGC[AT]GTTT. The deletion causes a frameshift, which changes a Methionine to a Valine at codon 1244 in the last exon of the protein, exon 20, and creates a premature stop codon at position 5 of the new reading frame. The last six amino acids of the protein are replaced by four incorrect amino acids, the clincal significance of which is unclear. The lost region is moderately conserved across species and is not within any known functional domain. This variant was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. No pathogenic variants have been reported in the lost region, to our knowledge. Based on the currently available information, we consider this deletion to be a variant of uncertain significance.
Invitae RCV000205061 SCV000260036 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-11-02 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BRIP1 gene (p.Met1244Valfs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acids of the BRIP1 protein. This variant is present in population databases (rs730881646, ExAC 0.03%). This variant has been observed in an individual affected with prostate cancer (PMID: 29356034). ClinVar contains an entry for this variant (Variation ID: 182368). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.
Ambry Genetics RCV000217493 SCV000276075 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-29 criteria provided, single submitter clinical testing Insufficient or Conflicting Evidence;Insufficient evidence

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