Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000466152 | SCV000547361 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2021-11-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1118 of the BRIP1 protein (p.Asn1118Ser). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 407862). 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 serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
St. |
RCV003153616 | SCV003843188 | uncertain significance | Familial cancer of breast | 2023-01-09 | criteria provided, single submitter | clinical testing | The BRIP1 c.3353A>G (p.Asn1118Ser) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with hereditary breast and ovarian cancer syndrome or Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |