Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129963 | SCV000184787 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-29 | criteria provided, single submitter | clinical testing | The p.D1868Y variant (also known as c.5602G>T), located in coding exon 10 of the BRCA2 gene, results from a G to T substitution at nucleotide position 5602. The aspartic acid at codon 1868 is replaced by tyrosine, an amino acid with highly dissimilar properties. In a study of 1854 high-risk BR/OV cancer families in Italy, this alteration was detected in 1 family (Azzollini J et al. Eur J Intern Med, 2016 Jul;32:65-71). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV001301982 | SCV001491169 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-09-12 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1868 of the BRCA2 protein (p.Asp1868Tyr). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 27062684). ClinVar contains an entry for this variant (Variation ID: 51889). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. 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. |
| University of Washington Department of Laboratory Medicine, |
RCV000129963 | SCV003848944 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| All of Us Research Program, |
RCV000113448 | SCV004846606 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-07-10 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with tyrosine at codon 1868 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 1 individual with a personal and/or family history of breast or ovarian cancer, this individual also carried a pathogenic variant in BRCA1 or BRCA2 that could explain the observed phenotype (PMID: 27062684). 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. |
| Breast Cancer Information Core |
RCV000113448 | SCV000146642 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing |