Submissions for variant NM_032043.3(BRIP1):c.608del (p.Asn203fs)

dbSNP: rs1603361570

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000821577	SCV000962339	pathogenic	Familial cancer of breast; Fanconi anemia complementation group J	2021-10-17	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). This variant has not been reported in the literature in individuals with BRIP1-related disease. This sequence change creates a premature translational stop signal (p.Asn203Thrfs*71) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product.
Color Diagnostics, LLC DBA Color Health	RCV001805901	SCV002052212	pathogenic	Hereditary cancer-predisposing syndrome	2021-05-17	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 6 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. To our knowledge, 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). Loss of BRIP1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics	RCV001805901	SCV003859913	pathogenic	Hereditary cancer-predisposing syndrome	2023-01-11	criteria provided, single submitter	clinical testing	The c.608delA pathogenic mutation, located in coding exon 5 of the BRIP1 gene, results from a deletion of one nucleotide at nucleotide position 608, causing a translational frameshift with a predicted alternate stop codon (p.N203Tfs*71). 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.	RCV003336219	SCV004045401	pathogenic	Familial cancer of breast	2023-05-31	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.