ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.868G>A (p.Gly290Ser) (rs145601931)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484748 SCV000566502 uncertain significance not provided 2015-05-06 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.868G>A at the cDNA level, p.Gly290Ser (G290S) at the protein level, and results in the change of a Glycine to a Serine (GGT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Gly290Ser was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glycine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRIP1 Gly290Ser occurs at a position that is conserved in mammals and is located in within the helicase ATP-binding domain (Cantor 2011, UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRIP1 Gly290Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Color RCV000775425 SCV000909788 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-13 criteria provided, single submitter clinical testing
Invitae RCV000823332 SCV000964186 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 290 of the BRIP1 protein (p.Gly290Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs145601931, ExAC 0.001%). This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 419001). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.