ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7822C>G (p.Pro2608Ala) (rs879255308)

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
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985252 SCV000296562 uncertain significance not provided 2018-12-13 criteria provided, single submitter clinical testing
Invitae RCV000474942 SCV000549859 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 2608 of the BRCA2 protein (p.Pro2608Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 252423). 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: 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.
Ambry Genetics RCV000567257 SCV000668522 likely benign Hereditary cancer-predisposing syndrome 2020-02-25 criteria provided, single submitter clinical testing Intact protein function observed in appropriate functional assay(s)
Counsyl RCV000239253 SCV000785284 uncertain significance Breast-ovarian cancer, familial 2 2017-06-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV000567257 SCV000905232 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-17 criteria provided, single submitter clinical testing This missense variant replaces proline with alanine at codon 2608 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). An RNA study showed no abnormal splicing (PMID: 32123317). This variant has been identified in an individual referred for genetic screening (PMID: 32123317). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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.