ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9190G>T (p.Asp3064Tyr) (rs80359177)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045743 SCV000073756 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-16 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 3064 of the BRCA2 protein (p.Asp3064Tyr). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs80359177, ExAC 0.002%). This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). However, in one of these individuals, a pathogenic allele was also identified in BRCA1, which suggests that this c.9190G>T variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 52773). 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"), but an algorithm developed specifically for the BRCA2 gene (PMID: 19043619), suggests that it is likely to be tolerated. However, these predictions have not been confirmed by published functional studies. 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 RCV000129844 SCV000184661 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000779948 SCV000916894 uncertain significance not specified 2018-12-24 criteria provided, single submitter clinical testing Variant summary: The variant, BRCA2 c.9190G>T (p.Asp3064Tyr) results in a non-conservative amino acid change located in the BRCA2, OB3 domain. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 277062 control chromosomes (gnomAD). 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.9190G>T in individuals affected with Hereditary Breast and Ovarian Cancer or experimental evidence demonstrating its impact on protein function have been reported in the literature. Co-occurrences with another pathogenic variant has been reported (BRCA1 c.5263_5264insC, p.Ser1755?fs), providing supporting evidence for a benign role. Two 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.
Breast Cancer Information Core (BIC) (BRCA2) RCV000114063 SCV000147563 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided 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.