Total submissions: 35
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000083150 | SCV000245217 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-01-12 | reviewed by expert panel | curation | Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.03455 (African), derived from 1000 genomes (2012-04-30). |
Invitae | RCV000045638 | SCV000073651 | benign | Hereditary breast ovarian cancer syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000083150 | SCV000154075 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2014-02-20 | criteria provided, single submitter | literature only | |
Gene |
RCV000120365 | SCV000167414 | benign | not specified | 2013-09-17 | 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 | RCV000131023 | SCV000185951 | benign | Hereditary cancer-predisposing syndrome | 2014-06-16 | 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. |
Michigan Medical Genetics Laboratories, |
RCV000083150 | SCV000196018 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2014-11-03 | criteria provided, single submitter | clinical testing | |
Pathway Genomics | RCV000083150 | SCV000223760 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2014-10-30 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000120365 | SCV000227872 | benign | not specified | 2014-07-15 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000120365 | SCV000301781 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000083150 | SCV000383792 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2018-01-29 | 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Laboratory Services, |
RCV000317148 | SCV000383793 | likely benign | Fanconi anemia complementation group D1 | 2018-01-29 | 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
A. |
RCV000413753 | SCV000492483 | uncertain significance | Breast neoplasm | criteria provided, single submitter | research | ||
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000045638 | SCV000494365 | benign | Hereditary breast ovarian cancer syndrome | 2014-01-20 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000120365 | SCV000538464 | benign | not specified | 2016-03-28 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ClinVar: Ben by expert panel |
Baylor Genetics | RCV000463955 | SCV000541026 | benign | Familial cancer of breast | 2017-02-23 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000034467 | SCV000602819 | benign | not provided | 2023-09-21 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131023 | SCV000684000 | benign | Hereditary cancer-predisposing syndrome | 2015-04-06 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000083150 | SCV000744550 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
National Health Laboratory Service, |
RCV000045638 | SCV002025862 | benign | Hereditary breast ovarian cancer syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | |
Genetics Program, |
RCV000045638 | SCV002515158 | benign | Hereditary breast ovarian cancer syndrome | 2021-11-01 | criteria provided, single submitter | research | |
Sema4, |
RCV000131023 | SCV002531978 | benign | Hereditary cancer-predisposing syndrome | 2020-04-28 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000120365 | SCV002551833 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002496514 | SCV002799481 | benign | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3 | 2021-08-10 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV000083150 | SCV004016880 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034467 | SCV000043233 | no known pathogenicity | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Benign. |
ITMI | RCV000120365 | SCV000084517 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Sharing Clinical Reports Project |
RCV000083150 | SCV000115224 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-05-01 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000083150 | SCV000147469 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000120365 | SCV000592232 | benign | not specified | no assertion criteria provided | clinical testing | The p.Ile2944Phe variant has been previously reported in the literature (Johnson 2007, Wagner 1999, Fackenthal 2005, Kim 2005). It has been previously identified in 6 out of 2146 proband chromosomes (frequency 0.003) in individuals with Breast Cancer, and in 3 out of 5110 control chromosomes (frequency 0.001). The Exome Variant Server has listed this variant in 1 out of 8599 genotype counts in a European American population, and 181 out 4225 genotype counts (frequency: 0.043) in an African American population, consistent with the observation that this variant was seen primarily in individuals of African decent in the literature above, and increasing the likelihood this is a common or benign polymorphism. This variant is listed in the BIC database under 115 entries as a variant with unknown clinical importance. It is also listed in the dbSNP database (ID#: rs4987047) with a minor allele frequency of 0.008 (1000 genomes) and up to 15% in some populations. The p.Ile2944 residue is conserved in the mammals and lower species examined, except in Opposum and Zebrafish where a Leucine (Leu) was present at this position, and increasing the likelihood an alteration to this residue may not have functional significance. In the UMD database, this variant has been identified in 1 out of 4 individuals with breast or ovarian cancers, where a second pathogenic BRCA2 mutation was also detected. In addition, this variant was previously identified by our laboratory in one individual who had a second pathogenic variant in the BRCA1 gene, increasing the likelihood the p.Ile2944Phe variant is benign. Computational analyses (AlignGVGD, PolyPhen2, SIFT, BLOSUM) provide inconsistent predictions regarding the impact to the protein; however, this information is not predictive enough to assume pathogenicity. However, functional studies including protein structure prediction, detection of full-length protein, no homologous recombination, no effect on splicing, and sensitivity to DNA damaging reagents, predict this variant to be "non-pathogenic" (Biswas 2012). Finally, Myriad reports this variant as a polymorphism (personal communication). In summary, the clinical significance of this variant cannot be determined with certainty at this time, although we would lean towards a more benign role for this variant. This variant is classified as Benign. | |
Diagnostic Laboratory, |
RCV000083150 | SCV000733325 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | no assertion criteria provided | clinical testing | ||
Mayo Clinic Laboratories, |
RCV000034467 | SCV000778720 | benign | not provided | 2017-10-11 | no assertion criteria provided | clinical testing | |
True Health Diagnostics | RCV000131023 | SCV000787956 | benign | Hereditary cancer-predisposing syndrome | 2017-11-14 | no assertion criteria provided | clinical testing | |
Laboratory of Diagnostic Genome Analysis, |
RCV000120365 | SCV001798936 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000120365 | SCV001906453 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000120365 | SCV001953738 | benign | not specified | no assertion criteria provided | clinical testing |