ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2594G>A (p.Arg865Gln) (rs781609846)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165535 SCV000216267 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000198650 SCV000255157 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 865 of the BRIP1 protein (p.Arg865Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs781609846, ExAC 0.02%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 186015). 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: "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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507155 SCV000602889 uncertain significance not specified 2016-09-01 criteria provided, single submitter clinical testing
Color RCV000165535 SCV001352717 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000507155 SCV001363543 uncertain significance not specified 2019-12-09 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.2594G>A (p.Arg865Gln) results in a conservative amino acid change located in the ATP-dependent helicase, C-terminal domain (IPR006555) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 252688 control chromosomes (gnomAD and Easton_2016). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2594G>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001199264 SCV001370327 uncertain significance Hereditary Cancer Syndrome 2019-05-10 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this varinat's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2. This variant was detected in heterozygous state.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.