Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568539 | SCV000661327 | likely benign | Hereditary cancer-predisposing syndrome | 2019-10-15 | 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. |
| Prevention |
RCV000679189 | SCV000805771 | uncertain significance | not provided | 2017-02-27 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000568539 | SCV000904092 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001232619 | SCV001405183 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-07-17 | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 479337). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 265 of the BRCA2 protein (p.Gly265Arg). This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon. |
| Baylor Genetics | RCV003476318 | SCV004211796 | uncertain significance | Familial cancer of breast | 2023-10-29 | criteria provided, single submitter | clinical testing |