Submissions for variant NM_032043.3(BRIP1):c.2772A>C (p.Glu924Asp)

dbSNP: rs730881625

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000160324	SCV000210825	uncertain significance	not provided	2014-05-21	criteria provided, single submitter	clinical testing	This variant is denoted BRIP1 c.2772A>C at the cDNA level, p.Glu924Asp (E924D) at the protein level, and results in the change of a Glutamic Acid to an Aspartic Acid (GAA>GAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Glu924Asp 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 Glutamic Acid and Aspartic Acid share similar properties, this is considered a conservative amino acid substitution. BRIP1 Glu924Asp occurs at a position that is well conserved across species and is located in the region of interaction with BRCA1 (Uniprot). In addition, 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 Glu924Asp is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV004609312	SCV005101094	uncertain significance	Hereditary cancer-predisposing syndrome	2024-06-06	criteria provided, single submitter	clinical testing	The p.E924D variant (also known as c.2772A>C), located in coding exon 18 of the BRIP1 gene, results from an A to C substitution at nucleotide position 2772. The glutamic acid at codon 924 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.