Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
MGZ Medical Genetics Center | RCV002290629 | SCV002579418 | likely pathogenic | Familial cancer of breast | 2021-08-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002561022 | SCV003442506 | likely pathogenic | Familial cancer of breast; Fanconi anemia complementation group J | 2023-07-14 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 3 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Fanconi anemia complementation group J (PMID: 16116423). ClinVar contains an entry for this variant (Variation ID: 929517). Studies have shown that this variant alters BRIP1 gene expression (PMID: 16116423). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.205+5G>A nucleotide in the BRIP1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Leiden Open Variation Database | RCV001194698 | SCV001364452 | pathogenic | Fanconi anemia complementation group J | 2011-02-07 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. |