ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.485G>A (p.Arg162Gln) (rs61757643)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129791 SCV000184600 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-28 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000424619 SCV000523740 uncertain significance not provided 2017-02-20 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.485G>A at the cDNA level, p.Arg162Gln (R162Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant was observed in a male with colon cancer; however, he also harbored a variant in MLH1 (Pearlman 2016) . BRIP1 Arg162Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. BRIP1 Arg162Gln occurs at a position that is conserved across species and is located in the Nuclear localization signal (Cantor 2001). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRIP1 Arg162Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000466396 SCV000547364 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 162 of the BRIP1 protein (p.Arg162Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs61757643, ExAC 0.009%). This variant has been observed to be homozygous in an individual who was not affected with Fanconi anemia (Invitae). It has also been observed in individuals with head and neck squamous cell carcinoma or colorectal cancer (PMID: 28678401, 27978560). ClinVar contains an entry for this variant (Variation ID: 141318). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000129791 SCV000689394 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-27 criteria provided, single submitter clinical testing
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

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