Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000679341 | SCV000149537 | likely benign | not provided | 2021-07-30 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 23056176, 26350354, 26787654, 27978560, 28301460) |
Ambry Genetics | RCV000115628 | SCV000186689 | likely benign | Hereditary cancer-predisposing syndrome | 2018-09-16 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |
Labcorp Genetics |
RCV000197435 | SCV000252706 | benign | Familial cancer of breast | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000197435 | SCV000427204 | likely benign | Familial cancer of breast | 2018-01-12 | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000679341 | SCV000600189 | benign | not provided | 2022-09-28 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000115628 | SCV000682763 | benign | Hereditary cancer-predisposing syndrome | 2015-09-22 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000197435 | SCV000786020 | likely benign | Familial cancer of breast | 2018-02-01 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000679341 | SCV000806120 | likely benign | not provided | 2016-10-03 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV003492479 | SCV000837942 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001818273 | SCV002071692 | benign | not specified | 2021-05-25 | criteria provided, single submitter | clinical testing | |
National Health Laboratory Service, |
RCV002225328 | SCV002505091 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000115628 | SCV002529586 | likely benign | Hereditary cancer-predisposing syndrome | 2021-03-14 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV000197435 | SCV004019252 | likely benign | Familial cancer of breast | 2023-02-24 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. |
CHEO Genetics Diagnostic Laboratory, |
RCV003492478 | SCV004240050 | likely benign | Breast and/or ovarian cancer | 2022-12-05 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001354852 | SCV001549564 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BARD1 p.Arg731Gly variant was identified in 1 of 2520 proband chromosomes (frequency: 0.0004) from individuals or families with Lynch syndrome (Yurgelun 2015). In addition, a functional study of SNPs in the BARD1 gene, using bioinformatics tools (such as in silico splicing, computational pathogenicity predictions, biochemical properties, energy minimization and RMSD) identified this variant as probably deleterious (Alshatwi 2012). The variant was also identified in the following databases: dbSNP (ID: rs76744638) as “With Uncertain significance allele”, ClinVar (4x, with conflicting interpretations, as likely benign by GeneDx and Ambry, benign by Invitae, uncertain significance by Illumina), Clinvitae (4x, with conflicting interpretations, as likely benign uncertain significance and benign), Cosmic (1x, as pathogenic in esophagus carcinoma), Zhejiang Colon Cancer Database (1x, "reported as pathogenic"). The variant was not identified in MutDB, database. The variant was identified in control databases in 174 of 277038 chromosomes at a frequency of 0.0006 in the following populations: African in 171 of 24028 chromosomes (freq. 0.007), Latino in 3 of 6460 chromosomes (freq. 0.00009), increasing the likelihood that this may be a low frequency variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). The p.Arg731 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. 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 uncertain significance. |