ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.485G>T (p.Arg162Leu) (rs61757643)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131634 SCV000186658 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-09 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000231093 SCV000291050 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-11-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 162 of the BRIP1 protein (p.Arg162Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs61757643, ExAC 0.03%). This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 142492). 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.
Counsyl RCV000662676 SCV000785383 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-07-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001174711 SCV001337982 uncertain significance not specified 2020-01-23 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.485G>T (p.Arg162Leu) results in a non-conservative amino acid change located in the Helicase-like, DEXD box c2 type domain 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 8e-06 in 251330 control chromosomes. 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.485G>T in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Color RCV000131634 SCV001343680 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-28 criteria provided, single submitter clinical testing

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.