ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.131G>A (p.Gly44Asp) (rs374730714)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164266 SCV000214891 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-13 criteria provided, single submitter clinical testing The p.G44D variant (also known as c.131G>A), located in coding exon 2 of the RAD51D gene, results from a G to A substitution at nucleotide position 131. The glycine at codon 44 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is not 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.
Counsyl RCV000411997 SCV000489176 uncertain significance Breast-ovarian cancer, familial 4 2016-08-30 criteria provided, single submitter clinical testing
Invitae RCV000411997 SCV000551345 uncertain significance Breast-ovarian cancer, familial 4 2019-11-07 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 44 of the RAD51D protein (p.Gly44Asp). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs374730714, ExAC 0.003%). This variant has been observed in an individual affected with ovarian cancer (PMID: 26261251). ClinVar contains an entry for this variant (Variation ID: 184924). Algorithms developed to predict the effect of missense changes on protein structure and function 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.
GeneDx RCV000590442 SCV000565463 uncertain significance not provided 2019-01-04 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.131G>A at the cDNA level, p.Gly44Asp (G44D) at the protein level, and results in the change of a Glycine to an Aspartic Acid (GGC>GAC). This variant has been observed in at least one woman with a history of epithelial ovarian cancer (Song 2015). RAD51D Gly44Asp was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the ssDNA binding domain (Kim 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether RAD51D Gly44Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000164266 SCV000686418 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590442 SCV000698090 uncertain significance not provided 2015-09-25 criteria provided, single submitter clinical testing

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