Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Evidence- |
RCV000661787 | SCV000784104 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-12-15 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
| Gene |
RCV000484185 | SCV000570704 | pathogenic | not provided | 2017-06-26 | criteria provided, single submitter | clinical testing | This deletion of 5 nucleotides in BRCA2 is denoted c.6986_6990delCGATT at the cDNA level and p.Pro2329HisfsX9 (P2329HfsX9) at the protein level. The normal sequence, with the bases that are deleted in braces, is GAGC[CGATT]ACCT. The deletion causes a frameshift which changes a Proline to a Histidine at codon 2329, and creates a premature stop codon at position 9 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. We consider this variant to be pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194390 | SCV001363898 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2019-08-09 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.6986_6990delCGATT (p.Pro2329HisfsX9) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250074 control chromosomes. To our knowledge, no occurrence of c.6986_6990delCGATT in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |