Submissions for variant NM_032043.3(BRIP1):c.1473+6A>G

gnomAD frequency: 0.00001  dbSNP: rs587780827

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000123349	SCV000166672	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2023-12-06	criteria provided, single submitter	clinical testing
Counsyl	RCV000411067	SCV000489885	uncertain significance	Fanconi anemia complementation group J	2016-07-08	criteria provided, single submitter	clinical testing
Counsyl	RCV000411739	SCV000489886	uncertain significance	Ovarian neoplasm	2016-07-08	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580346	SCV000684135	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-11	criteria provided, single submitter	clinical testing	This variant causes an A>G nucleotide substitution at the +6 position of intron 10 of the BRIP1 gene. Splice site prediction tools predict that this variant may not have a significant impact on RNA splicing. To our knowledge, RNA studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 7/235660 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.
Mendelics	RCV000411067	SCV000839380	uncertain significance	Fanconi anemia complementation group J	2018-07-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001618289	SCV001845635	benign	not provided	2015-08-17	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818297	SCV002065813	uncertain significance	not specified	2021-11-19	criteria provided, single submitter	clinical testing	DNA sequence analysis of the BRIP1 gene demonstrated a sequence change in intron 10, c.1473+6A>G. This sequence change has been described in the gnomAD database with a frequency of 0.06% in the Ashkenazi Jewish subpopulation (dbSNP rs587780827). Based on in-silico splice prediction programs, this sequence change may affect normal splicing of the BRIP1 gene, which would result in an abnormal protein, however functional studies have not been performed to prove this conclusively. This change does not appear to have been previously described in individuals with BRIP1-related disorders. It is possible that this sequence change represents a benign sequence change in the BRIP1 gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to this individual's disease phenotype cannot definitively be determined.
Sema4, Sema4	RCV000580346	SCV002531357	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-08	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV001818297	SCV002551192	likely benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003315825	SCV004019424	uncertain significance	Familial cancer of breast	2023-03-01	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.