Total submissions: 29
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000113572 | SCV001161523 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2019-06-18 | reviewed by expert panel | curation | IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000248 |
Invitae | RCV000044911 | SCV000072924 | benign | Hereditary breast ovarian cancer syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000129227 | SCV000183981 | benign | Hereditary cancer-predisposing syndrome | 2014-11-19 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: 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. |
Gene |
RCV000034453 | SCV000210627 | likely benign | not provided | 2020-09-28 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 21671020, 22713736, 24728327, 28477318, 28324225, 18284688, 30254663, 17972177, 25782689, 24323938, 24489791, 22703879, 21520273, 23469205, 23328489, 18627636, 20104584, 25777348, 26183948, 22874498, 15172753, 24504028, 28222693, 27376475, 29061375, 28664449, 28392550, 28651617, 29302806, 21218378, 27882536, 30093976, 32072338) |
CHEO Genetics Diagnostic Laboratory, |
RCV000735585 | SCV000219376 | benign | Breast and/or ovarian cancer | 2016-03-09 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000113572 | SCV000220889 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2014-11-16 | criteria provided, single submitter | literature only | |
Michigan Medical Genetics Laboratories, |
RCV000113572 | SCV000267793 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-04-21 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000113572 | SCV000383736 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Laboratory Services, |
RCV000384925 | SCV000383737 | likely benign | Fanconi anemia complementation group D1 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000044911 | SCV000494352 | benign | Hereditary breast ovarian cancer syndrome | 2015-04-30 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000129227 | SCV000683773 | likely benign | Hereditary cancer-predisposing syndrome | 2015-04-22 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000113572 | SCV000743318 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-07-28 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000113572 | SCV000744486 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000120335 | SCV000805739 | benign | not specified | 2017-08-17 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000034453 | SCV001248280 | benign | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | BRCA2: BP4, BS1, BS2 |
ARUP Laboratories, |
RCV000034453 | SCV002048634 | likely benign | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000129227 | SCV002536222 | benign | Hereditary cancer-predisposing syndrome | 2020-10-19 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000120335 | SCV002551712 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034453 | SCV000043220 | variant of unknown significance | not provided | 2012-07-13 | flagged submission | research | Converted during submission to Uncertain significance. |
ITMI | RCV000120335 | SCV000084487 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Breast Cancer Information Core |
RCV000113572 | SCV000146824 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000120335 | SCV000587835 | benign | not specified | 2014-01-31 | no assertion criteria provided | research | |
Department of Pathology and Laboratory Medicine, |
RCV000120335 | SCV000592042 | benign | not specified | no assertion criteria provided | clinical testing | The p.Arg2108Cys variant has been reported in the literature in 13/16,018 proband chromosomes from individuals with hereditary breast and/or ovarian cancer, although no control chromosomes were tested to establish the variant's frequency in the general population (Balia 2011, Capanu 2011, Purnomosari 2007, Borg 2010, Thirthagiri 2008, Jalkh 2012). There is conflicting evidence in the literature regarding its pathogenicity. It has been identified in the BIC database (x22) with unknown clinical importance, and in the LOVD and UMD databases (x5). The variant was identified in an individual who also had a pathogenic BRCA2 mutation c.5835_5842dup (p.Cys1948TyrfsX18) (UMD), and this finding increases the likelihood that the p.Arg2108Cys variant does not have clinical significance (notably compound heterozygous variants in the BRCA2 gene are expected to cause fanconi anemia but the phenotype was not provided in this case). In a functional assay that evaluated the effect of the transient overexpression of the p.Arg2108Cys variant on spontaneous homologous recombination (HR) in a HeLa cell line, the variant increased HR as much as a pathogenic variant G2748D, which led the authors to classify it as possibly pathogenic (Balia 2011), but the relevance of these findings in a cell model to the in-vivo organism remains questionable. It is listed in dbSNP database (ID#:rs55794205) as coming from a "clinical source" with a global minor allele frequency (MAF) of 0.002/5. Another variant at this position (p.Arg2108His) has been observed 126 times in the BIC database with unknown clinical significance, but this relatively high frequency may suggest that the variant is a common benign variant. In addition, this p.Arg2108 residue is not conserved in mammals and the variant amino acid Cys (Cysteine) is present in monkey, mouse, rat, cat and dog, increasing the likelihood that a change to this amino acid does not have functional significance. Computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein. However, this information is not very predictive of pathogenicity. Myriad genetics reports this variant as a polymorphism (personal communication). In summary, based on the above information. This variant meets our lab's criteria to be classified as benign. | |
Mayo Clinic Laboratories, |
RCV000034453 | SCV000778696 | likely benign | not provided | 2017-04-21 | no assertion criteria provided | clinical testing | |
Foulkes Cancer Genetics LDI, |
RCV000735585 | SCV000863723 | uncertain significance | Breast and/or ovarian cancer | 2013-03-15 | no assertion criteria provided | clinical testing | |
Clinical Genetics Laboratory, |
RCV000034453 | SCV001905985 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000034453 | SCV001956829 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Center for Precision Medicine, |
RCV002250502 | SCV002520819 | likely benign | Familial cancer of breast | no assertion criteria provided | literature only | ||
BRCAlab, |
RCV000113572 | SCV004243710 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2020-03-02 | no assertion criteria provided | clinical testing |