Total submissions: 25
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031088 | SCV000244332 | 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 = 0.00000998 |
Labcorp Genetics |
RCV000048067 | SCV000076080 | benign | Hereditary breast ovarian cancer syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000588855 | SCV000108664 | likely benign | not provided | 2020-07-26 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 24728327, 28717660, 28364669, 9333265, 26689913, 21990134, 15235020, 16267036, 22366370, 17924331, 10699917, 22753008) |
Ambry Genetics | RCV000129147 | SCV000183868 | 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 | RCV000031088 | SCV000220927 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2014-12-01 | criteria provided, single submitter | literature only | |
Genomic Diagnostic Laboratory, |
RCV000048067 | SCV000297226 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2015-12-03 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000129147 | SCV000537499 | likely benign | Hereditary cancer-predisposing syndrome | 2015-04-06 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588855 | SCV000699002 | benign | not provided | 2016-03-24 | criteria provided, single submitter | clinical testing | Variant summary: The variant of interest causes a missense change involving a non-conserved nucleotide with 3/4 in silico programs predicting a "benign" outcome (SNPs&GO not captured here due to low reliability index). The variant of interest was observed in a large, broad control population, ExAC with an overall allele frequency of 21/121360 (1/5780), however, the variant is predominantly observed in the Latino population with an allele frequency of 19/11576 (1/609), which exceeds the maximum expected allele frequency for a pathogenic BRCA1 variant of 1/1000. Therefore, suggesting that the variant of interest is a common polymorphism specifically found in population(s) of Latino origin. In addition, the variant of interest has been found in affected individuals, with limited co-occurrence and co-segregation information but has been observed to co-occur with another BRCA1 variant, c.5165C>T (p.Ser1722Phe), which was previously classified as VUS-possibly pathogenic and with a pathogenic BRCA2 variant c.771_775delTCAAA p.Asn257_Arg259fs indicating neutrality. Furthermore, the variant of interest has been classified by multiple reputable databases and clinical laboratories via ClinVar, along with publications, Easton_2007 and Lindor_2012, all which classify the variant as "neutral/likely neutral." Therefore, taking all available lines of evidence, the variant of interest is classified as Benign. |
Institute for Biomarker Research, |
RCV000129147 | SCV000803150 | likely benign | Hereditary cancer-predisposing syndrome | 2018-05-23 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000588855 | SCV000806928 | likely benign | not provided | 2018-01-11 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000031088 | SCV001287307 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2018-02-15 | 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 rule this variant out of causing disease. Therefore, this variant is classified as benign. |
ARUP Laboratories, |
RCV000588855 | SCV001471659 | likely benign | not provided | 2019-11-06 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000120292 | SCV002068141 | likely benign | not specified | 2020-09-14 | criteria provided, single submitter | clinical testing | |
National Health Laboratory Service, |
RCV000048067 | SCV002504998 | benign | Hereditary breast ovarian cancer syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000129147 | SCV002538181 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-26 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000120292 | SCV002551007 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002496475 | SCV002808066 | likely benign | Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S | 2021-11-29 | criteria provided, single submitter | clinical testing | |
Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003153310 | SCV003843369 | benign | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000031088 | SCV004815606 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2024-02-05 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000120292 | SCV004848548 | benign | not specified | 2021-05-17 | criteria provided, single submitter | clinical testing | The p.Arg1028His variant in BRCA1 is classified as benign because it has been identified in 0.3% (123/35432) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). Additionally, this variant is not conserved across species, and >5 mammals carry a histidine at this position despite high nearby amino acid conservation. In addition, computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1_Supporting, BP4. |
Ce |
RCV000588855 | SCV005093414 | likely benign | not provided | 2024-07-01 | criteria provided, single submitter | clinical testing | BRCA1: BP4, BS1 |
Sharing Clinical Reports Project |
RCV000031088 | SCV000053684 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2006-10-03 | no assertion criteria provided | clinical testing | |
ITMI | RCV000120292 | SCV000084444 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Breast Cancer Information Core |
RCV000031088 | SCV000144630 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000120292 | SCV000591424 | benign | not specified | no assertion criteria provided | clinical testing | The p.Arg1028 variant has been reported in the literature in 9/111500 proband chromosomes of individuals with HBOC and brain cancer, although no control chromosomes were tested to establish the frequency in the general population (Abkevich_2004, Judkins_2005a, Lindor_2012, Spitzer_2000). It has also been identified in the BIC (x13), BOCs (classified as ACMG 3), and LOVD databases. It is listed in the dbSNP database as coming from a "clinical source" (ID#: rs80357459) with a MAF score of 0.001 (1000 Genomes). This residue is not conserved in mammals and the variant amino acid Histidine (His) is present in the macaque at this position, increasing the likelihood that an alteration to this residue may not have functional significance. Computational analyses (PolyPhen, SIFT, AlignGVGD) do not predict any effect on the protein function, however, this information is not predictive enough to assume pathogenicity. Myriad reports this variant as being a "polymorphism" increasing the likelihood this variant does not have clinical significance. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of unknown significance. |