ClinVar Miner

Submissions for variant NM_024529.5(CDC73):c.668A>G (p.Asp223Gly)

gnomAD frequency: 0.00001  dbSNP: rs776394390
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000816013 SCV000956499 uncertain significance Parathyroid carcinoma 2018-11-08 criteria provided, single submitter clinical testing 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This sequence change replaces aspartic acid with glycine at codon 223 of the CDC73 protein (p.Asp223Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs776394390, ExAC 0.003%). This variant has not been reported in the literature in individuals with CDC73-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV004028872 SCV005028163 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-14 criteria provided, single submitter clinical testing The p.D223G variant (also known as c.668A>G), located in coding exon 7 of the CDC73 gene, results from an A to G substitution at nucleotide position 668. The aspartic acid at codon 223 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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