ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.923C>G (p.Ala308Gly)

gnomAD frequency: 0.00002  dbSNP: rs786203498
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166827 SCV000217641 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-22 criteria provided, single submitter clinical testing The p.A308G variant (also known as c.923C>G), located in coding exon 7 of the RAD51C gene, results from a C to G substitution at nucleotide position 923. The alanine at codon 308 is replaced by glycine, an amino acid with some similar properties. This variant was identified in a cohort of 3,579 African males diagnosed with prostate cancer who underwent multi-gene panel testing of 19 DNA repair and cancer predisposition genes (Matejcic M et al. JCO Precis Oncol 2020 Jan;4:32-43). This amino acid position is highly 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.
GeneDx RCV000235955 SCV000293351 uncertain significance not provided 2024-08-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 14704354)
Labcorp Genetics (formerly Invitae), Labcorp RCV000470112 SCV000550225 uncertain significance Fanconi anemia complementation group O 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 308 of the RAD51C protein (p.Ala308Gly). This variant is present in population databases (rs786203498, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 187133). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD51C protein function with a negative predictive value of 80%. 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.
Color Diagnostics, LLC DBA Color Health RCV000166827 SCV001340986 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-12 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002498827 SCV002813479 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O 2021-11-09 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004528918 SCV004104655 uncertain significance RAD51C-related disorder 2022-10-05 criteria provided, single submitter clinical testing The RAD51C c.923C>G variant is predicted to result in the amino acid substitution p.Ala308Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-56801419-C-G). This variant is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/187133/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003468794 SCV004207971 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2023-08-05 criteria provided, single submitter clinical testing

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