Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000484034 | SCV000567100 | pathogenic | not provided | 2018-09-19 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in BRIP1 is denoted c.1543delG at the cDNA level and p.Glu515LysfsX11 (E515KfsX11) at the protein level. The normal sequence, with the base that is deleted in brackets, is AAGA[delG]AAGT. The deletion causes a frameshift which changes a Glutamic Acid to a Lysine at codon 515, and creates a premature stop codon at position 11 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider this deletion to be pathogenic. |
Invitae | RCV002526540 | SCV003346692 | pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu515Lysfs*11) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). 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: 419356). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003335351 | SCV004045125 | pathogenic | Familial cancer of breast | 2023-06-02 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Baylor Genetics | RCV003335351 | SCV004211376 | likely pathogenic | Familial cancer of breast | 2021-06-04 | criteria provided, single submitter | clinical testing |