ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9564T>A (p.Asp3188Glu) (rs398122616)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160172 SCV000210510 uncertain significance not provided 2014-06-06 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9564T>A at the cDNA level, p.Asp3188Glu (D3188E) at the protein level, and results in the change of an Aspartic Acid to a Glutamic Acid (GAT>GAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asp3188Glu 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. Since Aspartic Acid and Glutamic Acid share similar properties, this is considered a conservative amino acid substitution. BRCA2 Asp3188Glu occurs at a position that is moderately conserved among mammals and is not located in a known functional domain. In addition, in silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Asp3188Glu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000703756 SCV000832671 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 3188 of the BRCA2 protein (p.Asp3188Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. 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 disease. ClinVar contains an entry for this variant (Variation ID: 91527). 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, 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.
Sharing Clinical Reports Project (SCRP) RCV000077044 SCV000108841 uncertain significance Breast-ovarian cancer, familial 2 2009-09-17 no assertion criteria provided clinical testing

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