ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5687C>A (p.Ala1896Glu) (rs730881539)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160096 SCV000210364 uncertain significance not provided 2014-01-20 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5687C>A at the cDNA level, p.Ala1896Glu (A1896E) at the protein level, and results in the change of an Alanine to a Glutamic Acid (GCA>GAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ala1896Glu 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. This variant is a non-conservative substitution in which a neutral non-polar amino acid is replaced with a negative polar one, altering a position that is moderately conserved throughout evolution and is not located in a known functional domain. In silico analyses predict this variant to have a benign effect on protein structure and function. Based on the currently available information, we consider BRCA2 Ala1896Glu to be a variant of uncertain significance.
Invitae RCV000168355 SCV000219044 uncertain significance Hereditary breast and ovarian cancer syndrome 2014-12-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 1896 of the BRCA2 protein (p.Ala1896Glu). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This sequence change has not been published in the literature and is not present in population databases. 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: "possibly_damaging"; Align-GVGD: "Class C0"). In summary, this is a novel missense change with uncertain impact on protein function. It has been 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.