Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022494 | SCV001184241 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-06 | criteria provided, single submitter | clinical testing | The p.D1482G variant (also known as c.4445A>G), located in coding exon 12 of the BRCA1 gene, results from an A to G substitution at nucleotide position 4445. The aspartic acid at codon 1482 is replaced by glycine, an amino acid with similar properties. In one study, this variant was observed in 1/1525 unrelated patients who had BRCA1/2 genetic testing due to a personal and/or family history suspicious for Hereditary Breast and/or Ovarian Cancer (Caux-Moncoutier V et al. Hum. Mutat., 2011 Mar;32:325-34). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001309906 | SCV001499420 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-07-19 | criteria provided, single submitter | clinical testing | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer syndrome (PMID: 21120943). ClinVar contains an entry for this variant (Variation ID: 808278). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 1482 of the BRCA1 protein (p.Asp1482Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. |
| MGZ Medical Genetics Center | RCV003607365 | SCV004543874 | uncertain significance | Familial cancer of breast | 2024-02-09 | criteria provided, single submitter | clinical testing | ACMG codes applied following ENIGMA VCEP rules: PM2_SUP |