Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001806763 | SCV002051151 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2021-12-16 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exon 19 in the BRCA2 gene. A presumed nomenclature of c.(8331+1_8332-1)_(8487+1_8488-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a large in-frame deletion in the BRCA2 gene, removing 52 amino acids (residues 2778-2829), which would affect the first oligonucleotide binding fold (OB1) domain (amino acids 2670-2795; IPR015187) of the BRCA2 protein. The variant was absent in 21692 control chromosomes (gnomAD structural variants dataset). The variant, c.(8331+1_8332-1)_(8487+1_8488-1)del, has been reported in the literature in at least one individual affected with breast cancer (Jimenez_2013). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, a different variant, c.8487+1G>A, which results in skipping of exon 19 of the BRCA2 protein has been classified as pathogenic by our laboratory. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |