Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000457812 | SCV000547280 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2022-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1024 of the BRIP1 protein (p.Gly1024Arg). This variant is present in population databases (rs147119272, gnomAD 0.006%). 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: 407819). 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 arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Ambry Genetics | RCV000570958 | SCV000664827 | likely benign | Hereditary cancer-predisposing syndrome | 2019-04-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Counsyl | RCV000662973 | SCV000785953 | uncertain significance | Fanconi anemia complementation group J; Ovarian neoplasm | 2018-01-19 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000570958 | SCV000911291 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-03 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003316562 | SCV004019302 | uncertain significance | Familial cancer of breast | 2023-02-27 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |