ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2120G>A (p.Arg707His) (rs200313471)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000583533 SCV000689315 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-17 criteria provided, single submitter clinical testing
GeneDx RCV000480168 SCV000571398 uncertain significance not provided 2016-08-18 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2120G>A at the cDNA level, p.Arg707His (R707H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant has been observed in at least one woman with a history of breast cancer (Tung 2016). BRIP1 Arg707His was not observed at a significant allele frequency in 1000 Genomes. Since Arginine and Histidine share similar properties, this is considered a conservative amino acid substitution. BRIP1 Arg707His occurs at a position that is conserved across species and is located within the Helicase domain (Cantor 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRIP1 Arg707His is a pathogenic or benign variant. We consider it to be a variant of uncertain.
Invitae RCV000702861 SCV000831733 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-08-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 707 of the BRIP1 protein (p.Arg707His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs200313471, ExAC 0.01%). This variant has been observed in an individual affected with breast cancer (PMID: 26976419). ClinVar contains an entry for this variant (Variation ID: 422038). 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: "Tolerated"; 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.

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