Total submissions: 30
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000111891 | SCV000244323 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-08-10 | 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 = 0.00018. Also class 1 based on frequency >1% in an outbred sampleset. Frequency 0.01399 (Asian), derived from 1000 genomes (2012-04-30). |
Labcorp Genetics |
RCV000047882 | SCV000075895 | benign | Hereditary breast ovarian cancer syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000123907 | SCV000167281 | benign | not specified | 2014-02-10 | 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 | RCV000162587 | SCV000213003 | benign | Hereditary cancer-predisposing syndrome | 2014-11-18 | 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. |
Counsyl | RCV000111891 | SCV000220480 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2014-07-04 | criteria provided, single submitter | literature only | |
Michigan Medical Genetics Laboratories, |
RCV000111891 | SCV000267703 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2016-04-21 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000111891 | SCV000403064 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2018-03-06 | 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Baylor Genetics | RCV000456795 | SCV000540988 | benign | Familial cancer of breast | 2017-02-23 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002477166 | SCV000575708 | likely benign | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S | 2022-05-21 | criteria provided, single submitter | clinical testing | |
Cancer Genetics and Genomics Laboratory, |
RCV000123907 | SCV000586886 | benign | not specified | 2017-04-18 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001811337 | SCV000602658 | benign | not provided | 2022-10-21 | criteria provided, single submitter | clinical testing | |
Institute for Biomarker Research, |
RCV000162587 | SCV000679703 | likely benign | Hereditary cancer-predisposing syndrome | 2017-07-12 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000162587 | SCV000683048 | benign | Hereditary cancer-predisposing syndrome | 2015-03-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000123907 | SCV000693608 | benign | not specified | 2017-11-01 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000111891 | SCV000744653 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000769715 | SCV000901135 | benign | Breast and/or ovarian cancer | 2016-03-03 | criteria provided, single submitter | clinical testing | |
National Health Laboratory Service, |
RCV000047882 | SCV002025997 | benign | Hereditary breast ovarian cancer syndrome | 2021-11-16 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000123907 | SCV002070422 | likely benign | not specified | 2019-11-18 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000162587 | SCV002538135 | benign | Hereditary cancer-predisposing syndrome | 2020-12-11 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000123907 | SCV002551016 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001811337 | SCV004009795 | benign | not provided | 2023-04-01 | criteria provided, single submitter | clinical testing | BRCA1: BS1, BS2 |
All of Us Research Program, |
RCV000111891 | SCV004815678 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2024-02-05 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV001811337 | SCV005251066 | benign | not provided | criteria provided, single submitter | not provided | ||
Breast Cancer Information Core |
RCV000111891 | SCV000144476 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2006-07-19 | no assertion criteria provided | clinical testing | |
Sharing Clinical Reports Project |
RCV000111891 | SCV000189333 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2011-02-25 | no assertion criteria provided | clinical testing | |
CSER _CC_NCGL, |
RCV000148383 | SCV000190081 | likely benign | Breast neoplasm | 2014-06-01 | no assertion criteria provided | research | |
Department of Pathology and Laboratory Medicine, |
RCV001353898 | SCV000591395 | benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA1 p.Tyr856His variant was identified in 21 of 4034 proband chromosomes (frequency: 0.0.005) from Korean, Malaysian and Japanese individuals or families with breast cancer, and was not identified in 718 control chromosomes from healthy individuals (Han S-H 2006, Thirthagiri 2008, Toh 2008, Mitsuru Emi 1998). The variant was (also) identified by our laboratory in 6 individuals with breast or ovarian cancer, with one individual in the presence of a second BRCA1 pathogenic variant (c.81-?_134+?del). In a functional complementation assay using BRCA1-deficient mouse embryonic stem cells, the variant was found to be neutral (Bouwman 2013). Promkan et al (2013), showed that BRCA1 (Tyr856His)-transfected mutant cells interfered with the function of wildtype BRCA1 by increased cellular proliferation, which may have implications for chemotherapeutic treatment. Multiple in silico prediction and evolutionary models show that the variant is neutral (Abkevich 2004, Burk-Herrick 2005, Lindor 2012, Spearman 2008, Tavtigian 2006) The variant was identified in dbSNP (ID: rs80356892) “With Likely benign allele”, Clinvitae database (classification benign/likely benign), Fanconi Anemia Mutation Database (LOVD), LOVD-IARC database, ARUP Laboratories BRCA Mutations Database (classification not pathogenic), the ClinVar database (classification benign, reviewed by an expert panel, submitters: ENIGMA, Ambry Genetics, Counsyl, Invitae, Gene Dx, Sharing Clinical Report Project (SCRP) (derived from Myriad reports), classification likely benign by CSER, and uncertain significance by BIC), GeneInsight COGR database (unclassified, “by a clinical laboratory(ies)”), the BIC database (18X with unknown clinical importance, pending classification), and UMD (6X with a “neutral” classification). The variant was also identified in 1000 Genomes Project in 15 of 5000 chromosomes (frequency: 0.003), HAPMAP-EAS in 14 of 1008 chromosomes (frequency: 0.0139), HAPMAP-AMR in 1 of 694 chromosomes (frequency: 0.0014), NHLBI GO Exome Sequencing Project (ESP) in 1 of 4406 African American alleles (frequency: 0.0002), and the the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015) in 184 of 121322 chromosomes (frequency: 0.0015) (or 180 individuals (3 homozygous) from a population of East Asian individuals, 3 South Asian and 1 Latino individual. In addition, this variant is classified as a polymorphism by Myriad (personal communication). The p.Tyr856 residue is not conserved in mammals and lower organisms, and the variant amino acid His is present in African clawed frog, increasing the likelihood that this variant does not have clinical significance. 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. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. | |
Clinical Genetics Laboratory, |
RCV000123907 | SCV001906054 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000123907 | SCV001956228 | benign | not specified | no assertion criteria provided | clinical testing | ||
Center for Precision Medicine, |
RCV000456795 | SCV002520885 | likely benign | Familial cancer of breast | no assertion criteria provided | curation |