Submissions for variant NM_032043.3(BRIP1):c.556A>G (p.Lys186Glu)

dbSNP: rs730881624

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000160321	SCV000210821	uncertain significance	not provided	2014-08-21	criteria provided, single submitter	clinical testing	This variant is denoted BRIP1 c.556A>G at the cDNA level, p.Lys186Glu (K186E) at the protein level, and results in the change of a Lysine to a Glutamic Acid (AAA>GAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Lys186Glu 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. Since Lysine and Glutamic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRIP1 Lys186Glu occurs at a position that is moderately conserved across species and is located within the nucleotide binding region of the Helicase ATP-binding domain. 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 Lys186Glu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV003162674	SCV003859889	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-15	criteria provided, single submitter	clinical testing	The p.K186E variant (also known as c.556A>G), located in coding exon 5 of the BRIP1 gene, results from an A to G substitution at nucleotide position 556. The lysine at codon 186 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.