Submissions for variant NM_032043.3(BRIP1):c.2531T>C (p.Leu844Pro)

dbSNP: rs1555574776

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000574404	SCV000661500	uncertain significance	Hereditary cancer-predisposing syndrome	2016-01-21	criteria provided, single submitter	clinical testing	The p.L844P variant (also known as c.2531T>C), located in coding exon 17 of the BRIP1 gene, results from a T to C substitution at nucleotide position 2531. The leucine at codon 844 is replaced by proline, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 120000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV001030533	SCV001193529	uncertain significance	Hereditary breast ovarian cancer syndrome	2019-05-01	criteria provided, single submitter	research
Color Diagnostics, LLC DBA Color Health	RCV000574404	SCV002053455	uncertain significance	Hereditary cancer-predisposing syndrome	2021-04-14	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with proline at codon 844 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.
Leiden Open Variation Database	RCV001194711	SCV001364477	uncertain significance	not provided	2019-08-13	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.