Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001188462 | SCV001355530 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with aspartic acid at codon 888 of the BRIP1 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 not been reported in individuals affected with BRIP1-related disorders in the literature. 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. |
| Invitae | RCV001216309 | SCV001388099 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-05-18 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 926079). 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. 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. This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 888 of the BRIP1 protein (p.His888Asp). |
| Ambry Genetics | RCV001188462 | SCV002744825 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-27 | criteria provided, single submitter | clinical testing | The p.H888D variant (also known as c.2662C>G), located in coding exon 18 of the BRIP1 gene, results from a C to G substitution at nucleotide position 2662. The histidine at codon 888 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is 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. |
| KCCC/NGS Laboratory, |
RCV003230644 | SCV003926636 | uncertain significance | Familial cancer of breast | 2023-05-29 | criteria provided, single submitter | clinical testing | a variant of uncertain significance was detected in the BRIP1 gene c.2662C>G. This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 888 of the BRIP1 protein (p.His888Asp). This variant is not present in population databases (gnomAD no frequency). This amino acid position is mild conserved (PhyloP=3.68) . This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 926079). this alteration is predicted to be tolerated by in silico analysis. 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. |
| Baylor Genetics | RCV003230644 | SCV004217039 | uncertain significance | Familial cancer of breast | 2023-07-29 | criteria provided, single submitter | clinical testing |