Total submissions: 29
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000119170 | SCV000153899 | benign | Fanconi anemia complementation group O | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000212938 | SCV000171271 | benign | not specified | 2014-04-03 | 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 | RCV000129159 | SCV000183887 | benign | Hereditary cancer-predisposing syndrome | 2014-07-28 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Prevention |
RCV000212938 | SCV000315331 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Counsyl | RCV000119170 | SCV000489839 | likely benign | Fanconi anemia complementation group O | 2016-06-10 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000411970 | SCV000489840 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 3 | 2016-06-10 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000129159 | SCV000537389 | benign | Hereditary cancer-predisposing syndrome | 2015-10-16 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000658791 | SCV000780586 | likely benign | not provided | 2024-10-01 | criteria provided, single submitter | clinical testing | RAD51C: BP4, BS2 |
Eurofins Ntd Llc |
RCV000212938 | SCV000854882 | benign | not specified | 2018-04-06 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000212938 | SCV000888596 | benign | not specified | 2020-08-14 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000119170 | SCV001140714 | likely benign | Fanconi anemia complementation group O | 2019-05-28 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000658791 | SCV001474259 | benign | not provided | 2023-10-09 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000658791 | SCV002010716 | likely benign | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001798373 | SCV002043686 | benign | Breast and/or ovarian cancer | 2019-05-15 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000212938 | SCV002066888 | benign | not specified | 2021-06-10 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000129159 | SCV002531812 | benign | Hereditary cancer-predisposing syndrome | 2020-05-20 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000212938 | SCV002551127 | likely benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Genetics and Molecular Pathology, |
RCV000411970 | SCV002761730 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 3 | 2020-10-19 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV000411970 | SCV004017245 | benign | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000411970 | SCV004043662 | benign | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-05-10 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. |
Center for Genomic Medicine, |
RCV000411970 | SCV004805808 | benign | Breast-ovarian cancer, familial, susceptibility to, 3 | 2024-03-29 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV000658791 | SCV005211128 | likely benign | not provided | criteria provided, single submitter | not provided | ||
True Health Diagnostics | RCV000129159 | SCV000788200 | likely benign | Hereditary cancer-predisposing syndrome | 2017-12-01 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001354932 | SCV001549661 | benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The RAD51C p.Ala126Thr variant was identified in 70 of 11449 proband chromosomes (frequency: 0.006) from individuals or families with hereditary breast and ovarian cancer (Akbari_2010_20723205, Blanco_2014_25086635, Clague_2011_21980511, Coulet_2013_22725699, Jonson_2015_26740214, Kushnir_2012_23117857, Leeneer_2012_22370629, Lu_2012_22476429, Meindl_2009_20400964, Romero_2011_ 21537932, Scheckenbach_2014_24315737, Thompson_2012_21990120, Vuorela_2011_21750962, Wong_2011_21409391). The variant was also identified in dbSNP (ID: rs61758784) as “With other allele”, ClinVar (as likely benign by PreventionGenetics and Counsyl, as benign by Invitae, GeneDx, Ambry Genetics, Color Genomics, and Quest Diagnostics), Clinvitae (as benign and likely benign), LOVD 3.0 (9x), and Zhejiang Colon Cancer Database (2x). The variant was not identified in Cosmic or MutDB databases. The variant was identified in control databases in 955 of 275828 chromosomes (3 homozygous) at a frequency of 0.003462 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 28 of 23954 chromosomes (freq: 0.001169), Other in 31 (1 homozygous) of 6444 chromosomes (freq: 0.004811), Latino in 109 (1 homozygous) of 34292 chromosomes (freq: 0.003179), European (Non-Finnish) in 684 (1 homozygous) of 125890 chromosomes (freq: 0.005433), Ashkenazi Jewish in 43 of 10090 chromosomes (freq: 0.004262), European (Finnish) in 8 of 25752 chromosomes (freq: 0.000311), and South Asian in 52 of 30556 chromosomes (freq: 0.001702), while the variant was not observed in the East Asian populations. The variant is classified as a benign polymorphism in the literature (Akbari_2010_20723205, Clague_2011_21980511, Coulet_2013_22725699, Jonson_2015_26740214, Kushnir_2012_23117857, Leeneer_2012_22370629, Lu_2012_22476429, Meindl_2009_20400964, Osorio_2012_22451500). In vivo yeast functional studies have shown no detectable difference in expression versus the wild type allele (Clague_2011_21980511). In addition, Jonson (2015_26740214) has reported that the variant to be co-occurring in three individuals with a disease-causing RAD51C (c.945dupT), BRCA1 (p.Gln563Ter) or BRCA2 (c.5164_5165delAG) mutation, increasing the likelihood that the p.Ala126Thr variant does not have clinical significance. The p.Ala126Thr residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 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. | |
Diagnostic Laboratory, |
RCV000658791 | SCV001740781 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000212938 | SCV001807201 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000658791 | SCV001905908 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000658791 | SCV001959252 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000658791 | SCV002035818 | likely benign | not provided | no assertion criteria provided | clinical testing |