ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.752A>G (p.Asp251Gly)

dbSNP: rs2048496443
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Hereditary Cancer Group, L’Institut d'Investigació Biomèdica de Bellvitge RCV001779208 SCV001623543 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2021-05-03 criteria provided, single submitter curation
Labcorp Genetics (formerly Invitae), Labcorp RCV002554102 SCV003020533 uncertain significance Fanconi anemia complementation group O 2023-04-22 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. 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. ClinVar contains an entry for this variant (Variation ID: 1098908). This missense change has been observed in individual(s) with breast cancer (PMID: 26976419). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 251 of the RAD51C protein (p.Asp251Gly).
Ambry Genetics RCV003298707 SCV003993238 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-27 criteria provided, single submitter clinical testing The p.D251G variant (also known as c.752A>G), located in coding exon 5 of the RAD51C gene, results from an A to G substitution at nucleotide position 752. The aspartic acid at codon 251 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a cohort of breast cancer patients (Tung N et al. J Clin Oncol, 2016 May;34:1460-8). 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.
Color Diagnostics, LLC DBA Color Health RCV003298707 SCV004357126 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-21 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 251 of the RAD51C 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 been reported in an individual affected with breast cancer in the literature (PMID: 26976419). 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.

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