Submissions for variant NM_032043.3(BRIP1):c.2339_2340del (p.Ile780fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV003334638	SCV004043123	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV004017984	SCV004848797	likely pathogenic	Hereditary breast ovarian cancer syndrome	2022-11-03	criteria provided, single submitter	clinical testing	The p.Ile780AsnfsX15 variant in BRIP1 has not been reported in individuals with breast and or ovarian cancer and was absent from large population databases. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 780 and leads to a premature termination codon 15 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the BRIP1 gene is an established disease mechanism in autosomal dominant breast and ovariant cancer. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant breast and ovarian cancer. ACMG/AMP Criteria applied: PVS1, PM2_Supporting.