ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2617A>T (p.Thr873Ser)

dbSNP: rs758444508
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216067 SCV000279730 uncertain significance not provided 2015-12-28 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2617A>T at the cDNA level, p.Thr873Ser (T873S) at the protein level, and results in the change of a Threonine to a Serine (ACC>TCC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Thr873Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Threonine and Serine share similar properties, this is considered a conservative amino acid substitution. BRIP1 Thr873Ser occurs at a position that is not conserved and is located in the Helicase domain (Cantor 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRIP1 Thr873Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854743 SCV002159996 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2021-11-22 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 234720). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 873 of the BRIP1 protein (p.Thr873Ser).

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.