Submissions for variant NM_032043.3(BRIP1):c.1144G>A (p.Asp382Asn)

dbSNP: rs1452168198

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001188578	SCV001355651	uncertain significance	Hereditary cancer-predisposing syndrome	2020-01-17	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with asparagine at codon 382 of the BRIP1 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/249164 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001307089	SCV001496482	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2021-09-01	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid with asparagine at codon 382 of the BRIP1 protein (p.Asp382Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics	RCV001188578	SCV002613690	uncertain significance	Hereditary cancer-predisposing syndrome	2024-08-24	criteria provided, single submitter	clinical testing	The p.D382N variant (also known as c.1144G>A), located in coding exon 8 of the BRIP1 gene, results from a G to A substitution at nucleotide position 1144. The aspartic acid at codon 382 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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.