Submissions for variant NM_032043.3(BRIP1):c.851T>C (p.Val284Ala)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003805590	SCV004588805	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2022-12-16	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRIP1 protein function. 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 valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 284 of the BRIP1 protein (p.Val284Ala).
Ambry Genetics	RCV004605049	SCV005101050	uncertain significance	Hereditary cancer-predisposing syndrome	2024-04-26	criteria provided, single submitter	clinical testing	The p.V284A variant (also known as c.851T>C), located in coding exon 6 of the BRIP1 gene, results from a T to C substitution at nucleotide position 851. The valine at codon 284 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.