ClinVar Miner

Submissions for variant NM_002878.4(RAD51D):c.136T>C (p.Ser46Pro)

dbSNP: rs980673532
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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 RCV000564118 SCV000663818 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-06 criteria provided, single submitter clinical testing The p.S46P variant (also known as c.136T>C), located in coding exon 2 of the RAD51D gene, results from a T to C substitution at nucleotide position 136. The serine at codon 46 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000564118 SCV000691307 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-08 criteria provided, single submitter clinical testing This missense variant replaces serine with proline at codon 46 of the RAD51D protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000801315 SCV000941088 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2023-03-07 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 480525). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 46 of the RAD51D protein (p.Ser46Pro).
GeneDx RCV003159135 SCV003853173 uncertain significance not provided 2022-09-30 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: 21111057)
PreventionGenetics, part of Exact Sciences RCV003420004 SCV004112852 uncertain significance RAD51D-related disorder 2022-12-09 criteria provided, single submitter clinical testing The RAD51D c.136T>C variant is predicted to result in the amino acid substitution p.Ser46Pro. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/480525/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV000801315 SCV004200410 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2023-06-06 criteria provided, single submitter clinical testing

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