Submissions for variant NM_032043.3(BRIP1):c.2732dup (p.Thr912fs)

gnomAD frequency: 0.00001  dbSNP: rs752780954

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000469617	SCV000547279	pathogenic	Familial cancer of breast; Fanconi anemia complementation group J	2024-04-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr912Aspfs*27) 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 (rs752780954, gnomAD 0.01%). 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: 407818). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000570668	SCV000668949	pathogenic	Hereditary cancer-predisposing syndrome	2024-11-12	criteria provided, single submitter	clinical testing	The c.2732dupT pathogenic mutation, located in coding exon 18 of the BRIP1 gene, results from a duplication of T at nucleotide position 2732, causing a translational frameshift with a predicted alternate stop codon (p.T912Dfs*27). This variant was reported in 3/60,466 breast cancer cases and in 2/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). 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.
GeneDx	RCV000657456	SCV000779191	pathogenic	not provided	2020-01-16	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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29922827)
Myriad Genetics, Inc.	RCV003335331	SCV004044346	pathogenic	Familial cancer of breast	2023-06-07	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Color Diagnostics, LLC DBA Color Health	RCV000570668	SCV004362902	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-13	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 19 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. In a large breast cancer case-control study, this variant has been reported in 3/60466 individuals affected with breast cancer and 2/53461 unaffected control individuals (PMID: 33471991). This variant has been identified in 12/251362 chromosomes 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000657456	SCV005089817	likely pathogenic	not provided	2024-07-31	criteria provided, single submitter	clinical testing
Centre for Clinical Genetics and Genomic Diagnostics, Zealand University Hospital	RCV000657456	SCV005328472	pathogenic	not provided	2024-08-07	criteria provided, single submitter	clinical testing
BRCAlab, Lund University	RCV003155943	SCV002588952	pathogenic	Ovarian cancer	2022-08-26	no assertion criteria provided	clinical testing