Submissions for variant NM_032043.3(BRIP1):c.905T>C (p.Leu302Pro)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002301727	SCV002589893	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2022-09-04	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 302 of the BRIP1 protein (p.Leu302Pro). This variant is not present in population databases (gnomAD 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: "Deleterious"; 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.
Color Diagnostics, LLC DBA Color Health	RCV003585246	SCV004362957	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-20	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with proline at codon 302 of the BRIP1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.
Ambry Genetics	RCV003585246	SCV005029286	uncertain significance	Hereditary cancer-predisposing syndrome	2024-02-28	criteria provided, single submitter	clinical testing	The p.L302P variant (also known as c.905T>C), located in coding exon 6 of the BRIP1 gene, results from a T to C substitution at nucleotide position 905. The leucine at codon 302 is replaced by proline, 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 alteration remains unclear.
GeneDx	RCV004591870	SCV005079646	uncertain significance	not provided	2024-07-12	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge