ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.752T>A (p.Ile251Lys) (rs778847822)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483141 SCV000565471 uncertain significance not provided 2018-11-07 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.752T>A at the cDNA level, p.Ile251Lys (I251K) at the protein level, and results in the change of an Isoleucine to a Lysine (ATA>AAA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. RAD51D Ile251Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the RAD51C binding domain (Miller 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51D Ile251Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000774916 SCV000908953 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-03 criteria provided, single submitter clinical testing
Invitae RCV001215380 SCV001387120 uncertain significance Breast-ovarian cancer, familial 4 2019-10-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with lysine at codon 251 of the RAD51D protein (p.Ile251Lys). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and lysine. This variant is present in population databases (rs778847822, ExAC 0.002%). This variant has not been reported in the literature in individuals with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 418446). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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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