ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.254C>T (p.Ser85Leu) (rs587781830)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130117 SCV000184948 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-07 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000198791 SCV000255154 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-01 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 85 of the BRIP1 protein (p.Ser85Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast and colorectal cancer (PMID: 26901136, 26921362). ClinVar contains an entry for this variant (Variation ID: 141545). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
GeneDx RCV000484594 SCV000568059 uncertain significance not provided 2018-12-19 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.254C>T at the cDNA level, p.Ser85Leu (S85L) at the protein level, and results in the change of a Serine to a Leucine (TCA>TTA). This variant was observed in at least one individual with rectal cancer (de Voer 2016). This variant was also observed in 1/ 1,313 breast cancer cases, but was absent from 1,123 controls (Easton 2016). BRIP1 Ser85Leu was not observed at a significant allele 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 evidence, it is unclear whether BRIP1 Ser85Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000130117 SCV000684220 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-12 criteria provided, single submitter clinical testing
Counsyl RCV000662486 SCV000784987 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-03-14 criteria provided, single submitter clinical testing

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