Submissions for variant NM_032043.3(BRIP1):c.2108delinsTCC (p.Lys703fs)

dbSNP: rs786203384

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166665	SCV000217470	pathogenic	Hereditary cancer-predisposing syndrome	2025-02-24	criteria provided, single submitter	clinical testing	The c.2108delAinsTCC pathogenic mutation, located in coding exon 14 of the BRIP1 gene, results from the deletion of one nucleotide and insertion of 3 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.K703Ifs*3). This mutation has previously been reported in multiple individuals and families affected with ovarian and/or breast cancer (Walsh T et al. Proc. Natl. Acad. Sci. U.S.A. 2011 Nov;108:18032-7; Helgadottir HT et al. Sci Rep, 2021 07;11:14737; Arvai KJ et al. Hered Cancer Clin Pract, 2019 Jul;17:19; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488; Norquist BM et al. JAMA Oncol, 2016 Apr;2:482-90; Kanchi KL et al. Nat Commun, 2014;5:3156), in a patient diagnosed with both breast and pancreatic cancers (Yurgelun MB et al. Genet Med, 2019 01;21:213-223), and in a patient with medulloblastoma (Waszak SM et al. Lancet Oncol. 2018 Jun;19:785-798). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000203877	SCV000259558	pathogenic	Familial cancer of breast; Fanconi anemia complementation group J	2025-01-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys703Ilefs*3) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). This variant is present in population databases (rs760863397, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with breast cancer, ovarian cancer, and/or pancreatic cancer (PMID: 22006311, 25452441, 26720728, 29961768). ClinVar contains an entry for this variant (Variation ID: 186992). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000485974	SCV000565781	pathogenic	not provided	2023-11-03	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17033622, 26689913, 22006311, 25452441, 26720728, 26681312, 26315354, 19763819, 23242139, 26921362, 29753700, 29961768, 30322717, 32782288, 16116423, 24448499, 21964575, 31341520, 34282249)
Color Diagnostics, LLC DBA Color Health	RCV000166665	SCV000689314	pathogenic	Hereditary cancer-predisposing syndrome	2025-01-21	criteria provided, single submitter	clinical testing	This variant replaces 1 nucleotide with 3 new nucleotides in exon 15 of the BRIP1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with ovarian cancer, breast cancer, and pancreatic cancer (PMID: 22006311, 24240112, 26720728, 29961768). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRIP1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Revvity Omics, Revvity	RCV003133158	SCV003810532	pathogenic	Fanconi anemia complementation group J	2020-09-11	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003335164	SCV004042885	pathogenic	Familial cancer of breast	2023-06-06	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics	RCV003335164	SCV004217050	pathogenic	Familial cancer of breast	2024-01-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000203877	SCV005654116	pathogenic	Familial cancer of breast; Fanconi anemia complementation group J	2024-03-08	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV003335164	SCV005874042	pathogenic	Familial cancer of breast	2024-10-07	criteria provided, single submitter	clinical testing	PVS1, PS4, PM2
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000203877	SCV006055120	pathogenic	Familial cancer of breast; Fanconi anemia complementation group J	2020-01-23	criteria provided, single submitter	clinical testing