Submissions for variant NM_032043.3(BRIP1):c.2857A>C (p.Thr953Pro)

dbSNP: rs587780245

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000116150	SCV000150059	uncertain significance	not provided	2014-02-15	criteria provided, single submitter	clinical testing	This variant is denoted BRIP1 c.2857A>C at the cDNA level, p.Thr953Pro (T953P) at the protein level, and results in the change of a Threonine to a Proline (ACC>CCC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Thr953Pro was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution in which a neutral polar amino acid is replaced with a neutral non-polar one, altering a position that is variable throughout evolution and is located in the BRCA1 binding domain (UniProt). In silico analyses predict this variant to have a benign effect on protein structure and function. Based on currently available information, it is unclear whether BRIP1 Thr953Pro is pathogenic or benign. We consider it to be a variant of uncertain significance. Furthermore, BRIP1 has been only recently described in association with cancer predisposition and the risks are not well understood.