ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.952G>A (p.Glu318Lys) (rs876658737)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218087 SCV000274389 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000523045 SCV000616846 uncertain significance not provided 2017-10-09 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.952G>A at the cDNA level, p.Glu318Lys (E318K) at the protein level,and results in the change of a Glutamic Acid to a Lysine (GAG>AAG). This variant has not, to our knowledge, beenpublished in the literature as pathogenic or benign. RAD51D Glu318Lys was not observed in large population cohorts(Lek 2016). Since Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51D Glu318Lys occurs at a position that is not conserved and is located inthe RAD51C binding domain (Miller 2004). In silico analyses are inconsistent regarding the effect this variant may haveon protein structure and function. Based on currently available evidence, it is unclear whether RAD51D Glu318Lys is apathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000819998 SCV000960690 uncertain significance Breast-ovarian cancer, familial 4 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 318 of the RAD51D protein (p.Glu318Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 230736). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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