Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000685639 | SCV000813126 | uncertain significance | Familial cancer of breast | 2021-11-05 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 565946). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 547 of the BARD1 protein (p.Glu547Ala). |
| Ambry Genetics | RCV001012530 | SCV001172995 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-02 | criteria provided, single submitter | clinical testing | The p.E547A variant (also known as c.1640A>C), located in coding exon 7 of the BARD1 gene, results from an A to C substitution at nucleotide position 1640. The glutamic acid at codon 547 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |