ClinVar Miner

Submissions for variant NM_002878.4(RAD51D):c.784C>A (p.Pro262Thr)

gnomAD frequency: 0.00001  dbSNP: rs1340405420
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000582769 SCV000691364 uncertain significance Hereditary cancer-predisposing syndrome 2021-01-25 criteria provided, single submitter clinical testing This missense variant replaces proline with threonine at codon 262 of the RAD51D protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 been identified in 2/282802 chromosomes 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.
GeneKor MSA RCV000582769 SCV000822183 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000698495 SCV000827162 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2024-04-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 262 of the RAD51D protein (p.Pro262Thr). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of RAD51D-related conditions (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 492444). 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 RAD51D 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.
GeneDx RCV001584402 SCV001811123 uncertain significance not provided 2020-09-11 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual undergoing hereditary cancer panel testing (Tsaousis 2019); This variant is associated with the following publications: (PMID: 31159747)
Ambry Genetics RCV000582769 SCV002669294 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-01 criteria provided, single submitter clinical testing The p.P262T variant (also known as c.784C>A), located in coding exon 9 of the RAD51D gene, results from a C to A substitution at nucleotide position 784. The proline at codon 262 is replaced by threonine, an amino acid with highly similar properties. This alteration has been reported in 1/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000698495 SCV005054006 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2024-02-15 criteria provided, single submitter clinical testing

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