ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1208G>A (p.Arg403Gln) (rs786202780)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165766 SCV000216511 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000165766 SCV000906531 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-08 criteria provided, single submitter clinical testing
GeneDx RCV000483464 SCV000569510 uncertain significance not provided 2017-06-06 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1208G>A at the cDNA level, p.Arg403Gln (R403Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Arg403Gln was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. BRIP1 Arg403Gln occurs at a position that is conserved across species and is not located within a known functional domain. 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 Arg403Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000459631 SCV000547286 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 403 of the BRIP1 protein (p.Arg403Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 186213). Algorithms developed to predict the effect of missense changes on protein structure and function 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.

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