Submissions for variant NM_032043.3(BRIP1):c.2111T>A (p.Leu704Ter)

dbSNP: rs1057517643

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000411722	SCV000489963	likely pathogenic	Fanconi anemia complementation group J	2016-08-29	criteria provided, single submitter	clinical testing
Counsyl	RCV000409317	SCV000489964	likely pathogenic	Ovarian neoplasm	2016-08-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000636132	SCV000757564	pathogenic	Familial cancer of breast; Fanconi anemia complementation group J	2023-12-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu704*) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 372090). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001267955	SCV001446481	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002418233	SCV002726995	pathogenic	Hereditary cancer-predisposing syndrome	2024-06-05	criteria provided, single submitter	clinical testing	The p.L704* pathogenic mutation (also known as c.2111T>A), located in coding exon 14 of the BRIP1 gene, results from a T to A substitution at nucleotide position 2111. This changes the amino acid from a leucine to a stop codon within coding exon 14. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Myriad Genetics, Inc.	RCV003316518	SCV004019321	pathogenic	Familial cancer of breast	2023-02-27	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein	RCV003316518	SCV004167623	pathogenic	Familial cancer of breast	2022-12-08	no assertion criteria provided	clinical testing