ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.262_264delTGT (rs587781388)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129221 SCV000183974 uncertain significance Hereditary cancer-predisposing syndrome 2012-12-20 criteria provided, single submitter clinical testing Insufficient or inconclusive evidence
GeneDx RCV000587394 SCV000210868 uncertain significance not provided 2018-12-30 criteria provided, single submitter clinical testing This in-frame deletion of three nucleotides in BRIP1 is denoted c.262_264delTGT at the cDNA level and p.Cys88del (C88del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TTGT[delTGT]GCAT. This variant has been observed in at least one individual with breast cancer and in two individuals with pancreatic cancer (Tung 2016, Shindo 2017). BRIP1 Cys88del was not observed at a significant allele frequency in large population cohorts (Lek 2016). This deletion of a single Cysteine amino acid is not located in a known functional domain. In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Since in-frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider BRIP1 Cys88del to be a variant of uncertain significance.
Invitae RCV000206278 SCV000259403 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-19 criteria provided, single submitter clinical testing This variant, c.262_264delTGT, results in the deletion of 1 amino acid of the BRIP1 protein (p.Cys88del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587781388, ExAC 0.01%). This variant has been reported in an individual affected with breast cancer (PMID: 26976419). This variant has also been observed in individuals affected with pancreatic ductal adenocarcinoma (PMID: 28767289). ClinVar contains an entry for this variant (Variation ID: 140945). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid 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 RCV000221468 SCV000275369 uncertain significance Tumor susceptibility linked to germline BAP1 mutations 2015-12-20 criteria provided, single submitter clinical testing
Color RCV000129221 SCV000684228 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587394 SCV000699700 uncertain significance not provided 2015-11-25 criteria provided, single submitter clinical testing
Leiden Open Variation Database RCV000587394 SCV001364454 uncertain significance not provided 2019-08-13 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.

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