ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.208G>A (p.Asp70Asn) (rs142189122)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115811 SCV000185442 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000115811 SCV000686428 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-09 criteria provided, single submitter clinical testing
GeneDx RCV000212955 SCV000149720 uncertain significance not provided 2018-09-13 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.208G>A at the cDNA level, p.Asp70Asn (D70N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). This variant has been observed in at least one individual with ovarian cancer and one individual with colorectal cancer (Song 2015, Yurgelun 2017). RAD51D Asp70Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the XRCC2 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 Asp70Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000285986 SCV000401970 uncertain significance Breast and Ovarian Cancer Susceptibility 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000464081 SCV000551346 uncertain significance Breast-ovarian cancer, familial 4 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 70 of the RAD51D protein (p.Asp70Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs142189122, ExAC 0.005%). This variant has been reported in an individual affected with ovarian cancer (PMID: 26261251), and an individual with colon cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 127885). 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: "Possibly Damaging"; 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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