ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.752G>A (p.Arg251His) (rs780834054)

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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 RCV000222495 SCV000276360 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence
Color RCV000222495 SCV000689416 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000692424 SCV000895115 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000280552 SCV000329152 uncertain significance not provided 2015-11-16 criteria provided, single submitter clinical testing This variant has not, to our knowledge, been published in the literature as either a pathogenic variant or a benign polymorphism. BRIP1 Arg251His was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Arginine and Histidine share similar properties, this is considered a conservative amino acid substitution. BRIP1 Arg251His alters a position that is highly conserved across species and is located within the helicase ATP-binding domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BRIP1 Arg251His is a pathogenic or a benign variant.
Invitae RCV000692424 SCV000820249 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-01-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 251 of the BRIP1 protein (p.Arg251His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs780834054, ExAC 0.004%). This variant has been reported in an individual with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 232270). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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