ClinVar Miner

Submissions for variant NM_002878.4(RAD51D):c.767A>C (p.Asp256Ala)

gnomAD frequency: 0.00001  dbSNP: rs371350110
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236920 SCV000293793 uncertain significance not provided 2016-01-05 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.767A>C at the cDNA level, p.Asp256Ala (D256A) at the protein level, and results in the change of an Aspartic Acid to an Alanine (GAC>GCC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Asp256Ala was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Aspartic Acid and Alanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51D Asp256Ala occurs at a position that is conserved in mammals and is located in the ATPase domain (Kim 2011). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether RAD51D Asp256Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV001026702 SCV001189133 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-29 criteria provided, single submitter clinical testing The p.D256A variant (also known as c.767A>C), located in coding exon 9 of the RAD51D gene, results from an A to C substitution at nucleotide position 767. The aspartic acid at codon 256 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002518459 SCV003504890 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2024-06-12 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 256 of the RAD51D protein (p.Asp256Ala). This variant is present in population databases (rs371350110, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 246302). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD51D protein function with a negative predictive value of 80%. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.