Submissions for variant NM_032043.3(BRIP1):c.3651G>T (p.Trp1217Cys)

dbSNP: rs542698396

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129907	SCV000184725	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-26	criteria provided, single submitter	clinical testing	The p.W1217C variant (also known as c.3651G>T), located in coding exon 19 of the BRIP1 gene, results from a G to T substitution at nucleotide position 3651. The tryptophan at codon 1217 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a cohort of 488 patients with breast cancer who were tested with a 25-gene panel test (Tung N et al. J. Clin. Oncol., 2016 May;34:1460-8). This alteration was detected in two different cohorts of Brazilian breast cancer patients (Sandoval RL et al. PLoS One, 2021 Feb;16:e0247363; Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This alteration was also detected in a patient with colorectal cancer who was also found to carry a pathogenic mutation in the MSH2 gene (Ricker CN et al. Cancer, 2017 Oct;123:3732-3743). This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000227303	SCV000291046	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000657056	SCV000567861	uncertain significance	not provided	2024-04-05	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 36451132, 35264596, 28640387, 26976419, 29625052, 33606809, 35980532, 35534704)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000657056	SCV000600918	uncertain significance	not provided	2020-10-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000657056	SCV000807147	uncertain significance	not provided	2016-11-02	criteria provided, single submitter	clinical testing
Mendelics	RCV003492594	SCV000839346	likely benign	Hereditary cancer	2024-01-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000227303	SCV000896645	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2018-10-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129907	SCV000911032	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-23	criteria provided, single submitter	clinical testing	This missense variant replaces tryptophan with cysteine at codon 1217 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with breast cancer (PMID: 26976419). This variant has been identified in 2/250810 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.
Molecular Diagnostics Laboratory, Barretos Cancer Hospital	RCV000989972	SCV002320684	likely benign	Familial cancer of breast	2022-03-28	criteria provided, single submitter	clinical testing	ACMG criteria: PM2, PS4_MODERADO, BP4, BP2. *Co-occurrence of pathogenic variant (c.2808_2811del) in BRCA2 gene.
Baylor Genetics	RCV000989972	SCV005059209	uncertain significance	Familial cancer of breast	2024-03-29	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV004595931	SCV005089741	uncertain significance	not specified	2024-07-31	criteria provided, single submitter	clinical testing