ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.407A>G (p.Asp136Gly) (rs768197423)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216846 SCV000276404 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
GeneDx RCV000235687 SCV000293768 uncertain significance not specified 2017-05-02 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.407A>G at the cDNA level, p.Asp136Gly (D136G) at the protein level, and results in the change of an Aspartic Acid to a Glycine (GAT>GGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Asp136Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Aspartic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51D Asp136Gly occurs at a position that is conserved across species and is located in the ATPase domain (Kim 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether RAD51D Asp136Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000461662 SCV000551323 uncertain significance Breast-ovarian cancer, familial 4 2018-08-16 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 136 of the RAD51D protein (p.Asp136Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs768197423, ExAC 0.009%). This variant has been reported in an individual affected with endometrial cancer (PMID: 27443514). ClinVar contains an entry for this variant (Variation ID: 232305). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000216846 SCV000691338 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-25 criteria provided, single submitter clinical testing

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