ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.878A>G (p.Asn293Ser) (rs746599076)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000319358 SCV000329153 uncertain significance not provided 2018-08-07 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.878A>G at the cDNA level, p.Asn293Ser (N293S) at the protein level, and results in the change of an Asparagine to a Serine (AAC>AGC). This variant was observed in an individual with uterine corpus endometrial carcinoma (Lu 2015). BRIP1 Asn293Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located within a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRIP1 Asn293Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000573698 SCV000661491 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-08 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000636175 SCV000757607 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 293 of the BRIP1 protein (p.Asn293Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs746599076, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 279708). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000319358 SCV000889229 uncertain significance not provided 2017-10-10 criteria provided, single submitter clinical testing
Color RCV000573698 SCV001355685 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-03 criteria provided, single submitter clinical testing

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