Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001190605 | SCV001358122 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-02 | criteria provided, single submitter | clinical testing | This variant causes a deletion encompassing the last 106 bases of exon 10 and the intron 10 splice donor site in the BRCA1 gene. To our knowledge, functional studies have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. However, a canonical intron 10 splice site variant (c.4096+1G>A) has been reported to reduce full-length BRCA1 transcript level (PMID: 17011978) and also has been reported in multiple individuals affected with breast cancer (PMID: 21156238, 23239986, 27328445, 29116469, 30728895) and ovarian cancer (PMID: 17011978, 24131973). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Invitae | RCV002560087 | SCV003228696 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-01-12 | 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. Experimental studies have shown that disruption of this donor splice site alters splicing of exon 10 (also referred to as exon 11 in the literature), resulting in loss of the full-length transcript, and increased expression of a shorter in-frame transcript that lacks a large portion of exon 10 (referred to as del11q) (PMID: 17011978, Invitae). This alternative in-frame transcript has been reported to occur naturally in healthy individuals (PMID: 24569164), and functional studies suggest that protein made from this transcript may retain residual function (PMID: 8972225, 11359908, 11431698, 16943438). The clinical significance of these findings is uncertain. ClinVar contains an entry for this variant (Variation ID: 927378). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant results in the deletion of part of exon 10 (c.3991_4096+10delinsAT) of the BRCA1 gene. It is expected to disrupt RNA splicing. |