ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.186A>G (p.Gln62=)

gnomAD frequency: 0.00322  dbSNP: rs28363303
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212933 SCV000171269 benign not specified 2014-03-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000131123 SCV000186054 benign Hereditary cancer-predisposing syndrome 2014-11-25 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV000203729 SCV000261112 benign Fanconi anemia complementation group O 2021-12-18 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000212933 SCV000315330 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000203729 SCV000404319 likely benign Fanconi anemia complementation group O 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services,Illumina RCV000412091 SCV000404320 likely benign Breast-ovarian cancer, familial, susceptibility to, 3 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Counsyl RCV000203729 SCV000489811 benign Fanconi anemia complementation group O 2016-05-25 criteria provided, single submitter clinical testing
Counsyl RCV000412091 SCV000489812 benign Breast-ovarian cancer, familial, susceptibility to, 3 2016-05-25 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212933 SCV000602137 likely benign not specified 2017-02-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000131123 SCV000686330 benign Hereditary cancer-predisposing syndrome 2015-08-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586849 SCV000699797 benign not provided 2016-07-01 criteria provided, single submitter clinical testing Variant summary: The c.186A>G (p.GLn62=) in RAD51C gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.001(123/121184 chrs tested), predominantly in individuals of African origin (0.01; 117/10292 control chrs). This frequency greatly exceeds the maximal expected frequency of a pathogenic allele (0.00006) in this gene. The variant of interest has been reported in several affected individuals in co-occurrence with known pathogenic variant in BRCA2 gene in at least 1HBOC family. In addition, the variant has been classified as Benign by reputable databases/clinical laboratory. Taking together, the variant was classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586849 SCV000888594 benign not provided 2018-07-11 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000212933 SCV002066303 likely benign not specified 2021-10-01 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000131123 SCV000788199 likely benign Hereditary cancer-predisposing syndrome 2017-09-13 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355321 SCV001550179 benign Malignant tumor of breast no assertion criteria provided clinical testing The RAD51C p.Gln62= variant was identified in 3 of 4196 proband chromosomes (frequency: 0.001) from American, Danish and Spanish individuals or families with non-BRCA1/2 hereditary breast/ovarian cancer (Zheng_2010_20697805, Romero_2011_21537932, Jonson_2015_26740214, Clague_2011_21980511). In 1 proband, the variant co-occurred with a disease-causing BRCA2 mutation (p.Lys172Lys) (Jonson_2015_26740214). The variant was also identified in dbSNP (ID: rs28363303) “With Likely benign allele”, ClinVar (classified benign by GeneDx, Ambry Genetics, Invitae, Prevention Genetics, Counsyl, and likely benign by Illumina, and Quest Diagnostics Nichols Institute San Juan), and Clinvitae (6x) but was not identified in Cosmic, MutDB, or LOVD 3.0. The variant was identified in control databases in 279 (1 homozygous) of 277224 chromosomes at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 254 of 24038 chromosomes (freq: 0.01), Latino in 18 of 34420 chromosomes (freq: 0.0005), European Non-Finnish in 5 of 126712 chromosomes (freq: 0.00004), and South Asian in 2 of 30776 chromosomes (freq: 0.00007), while not observed in the Other, Ashkenazi Jewish, East Asian, and European Finnish populations. The p.Gln62= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

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