Submissions for variant NM_002878.4(RAD51D):c.766del (p.Asp256fs)

dbSNP: rs1597856162

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000822827	SCV000963644	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 4	2018-11-06	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with RAD51D-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the RAD51D gene (p.Asp256Thrfs*54). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 73 amino acids of the RAD51D protein. This variant is expected to disrupt amino acid residues Asp256-Thr328 of the RAD51D protein, thereby removing the C-terminus of the ATPase domain (PMID: 14704354, 19327148, 21111057). Although functional studies have not been done for this particular variant, experimental studies using yeast two-hybrid analysis have shown that the region of the RAD51D protein necessary for RAD51C complexing localizes to the last ~100 amino acids (PMID: 10749867, 14704354, 19327148). The data indicates that this variant likely disrupts this important RAD51D-RAD51C interaction. 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.
Myriad Genetics, Inc.	RCV000822827	SCV004189603	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 4	2023-11-30	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.