ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.258_269del (p.Cys87_Cys90del) (rs730881648)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235146 SCV000210867 uncertain significance not provided 2018-01-29 criteria provided, single submitter clinical testing This in-frame deletion of 12 nucleotides in BRIP1 is denoted c.258_269del12 at the cDNA level and p.Cys87_C90del (C87_C90del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CATG[del12]CCAT. This variant has been observed in at least one individual undergoing hereditary cancer testing (Yorczyk 2015). BRIP1 c.258_269del12 was not observed at a significant allele frequency in large population cohorts (Lek 2016). The four deleted residues (Cysteine, Cysteine, Alanine, and Cysteine) are 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 c.258_269del12 to be a variant of uncertain significance.
Ambry Genetics RCV000160361 SCV000214008 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000225968 SCV000291017 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-10-14 criteria provided, single submitter clinical testing This sequence change deletes 12 nucleotides from exon 4 of the BRIP1 mRNA (c.258_269delTTGTTGTGCATG). This leads to the deletion of 4 amino acid residues in the BRIP1 protein (p.Cys87_Cys90del) but otherwise preserves the integrity of the reading frame. The frequency data for this variant (rs730881648) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has been reported in an individual with a personal and/or family history of cancer (PMID: 25318351). ClinVar contains an entry for this variant (Variation ID: 182370). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids 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.
Counsyl RCV000412087 SCV000490075 uncertain significance Fanconi anemia, complementation group J 2016-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000409620 SCV000490076 uncertain significance Neoplasm of ovary 2016-10-31 criteria provided, single submitter clinical testing
Color RCV000160361 SCV000684225 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235146 SCV000887989 uncertain significance not provided 2017-11-24 criteria provided, single submitter clinical testing

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