ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.4G>A (p.Gly2Ser) (rs372082751)

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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 RCV000563634 SCV000667150 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000160955 SCV000211663 uncertain significance not provided 2014-09-02 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.4G>A at the cDNA level, p.Gly2Ser (G2S) at the protein level, and results in the change of a Glycine to a Serine (GGC>AGC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Gly2Ser was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Glycine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51D Gly2Ser occurs at a position that is well conserved across species and is located a region that preferentially binds single stranded DNA (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether RAD51D Gly2Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000554222 SCV000651755 uncertain significance Breast-ovarian cancer, familial 4 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2 of the RAD51D protein (p.Gly2Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs372082751, ExAC 0.01%) but has not been reported in the literature in individuals with a RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 182866). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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