Submissions for variant NM_032043.3(BRIP1):c.87G>T (p.Met29Ile)

dbSNP: rs769585673

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000570903	SCV000668909	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-20	criteria provided, single submitter	clinical testing	The p.M29I variant (also known as c.87G>T), located in coding exon 1 of the BRIP1 gene, results from a G to T substitution at nucleotide position 87. The methionine at codon 29 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported with a carrier frequency of 0.00092 in 7636 unselected prostate cancer patients and 0.00089 in 12366 male controls of Japanese ancestry (Momozawa Y et al. J. Natl. Cancer Inst., 2020 04;112:369-376). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000691171	SCV000818916	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2024-01-05	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 29 of the BRIP1 protein (p.Met29Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with prostate cancer (PMID: 31214711). ClinVar contains an entry for this variant (Variation ID: 483161). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRIP1 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health	RCV000570903	SCV000913101	uncertain significance	Hereditary cancer-predisposing syndrome	2018-12-30	criteria provided, single submitter	clinical testing
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV001030547	SCV001193543	uncertain significance	Hereditary breast ovarian cancer syndrome	2019-05-01	criteria provided, single submitter	research
Sema4, Sema4	RCV000570903	SCV002529242	uncertain significance	Hereditary cancer-predisposing syndrome	2021-12-10	criteria provided, single submitter	curation
GeneDx	RCV001194697	SCV004169551	uncertain significance	not provided	2023-05-08	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31214711, 32980694)
Baylor Genetics	RCV004569201	SCV005059928	uncertain significance	Familial cancer of breast	2023-12-17	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV001194697	SCV001364451	uncertain significance	not provided	2019-08-13	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.