Submissions for variant NM_032043.3(BRIP1):c.485G>A (p.Arg162Gln)

dbSNP: rs61757643

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129791	SCV000184600	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-09	criteria provided, single submitter	clinical testing	The p.R162Q variant (also known as c.485G>A), located in coding exon 4 of the BRIP1 gene, results from a G to A substitution at nucleotide position 485. The arginine at codon 162 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been identified in one individual from a North American cohort of individuals diagnosed with early onset colon cancer (Pearlman R et al. JAMA Oncol. 2017 Apr;3:464-471) and in one patient from a study consisting of 417 individuals with head and neck squamous cell carcinoma diagnosed before age 50 undergoing genetic testing of 16 Fanconi anemia genes (Chandrasekharappa SC et al. Cancer 2017 Oct;123:3943-3954). This variant was not present in a large cohort of 6341 breast cancer patients and 706 ovarian cancer patients, but was identified in 2/36687 controls (Weber-Lassalle N et al. Breast Cancer Res. 2018 Jan;20:7). 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.
GeneDx	RCV000424619	SCV000523740	uncertain significance	not provided	2023-06-21	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27978560, 29507082, 28678401, 29368626, 31822803, 11301010)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000466396	SCV000547364	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2024-01-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129791	SCV000689394	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-19	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 162 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRIP1_000689) and an unaffected individual and absent in suspected hereditary breast and ovarian cancer families (PMID: 29368626). This variant also has been reported in individuals affected with head and neck carcinoma and metastatic osteosarcoma (PMID: 28678401, 29507082). This variant has been identified in 3/251330 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.
Fulgent Genetics, Fulgent Genetics	RCV000466396	SCV000895117	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2018-10-31	criteria provided, single submitter	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV003387768	SCV004099490	uncertain significance	Familial cancer of breast	2023-10-30	no assertion criteria provided	clinical testing