Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000045064 | SCV000073077 | benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000074551 | SCV000108636 | likely benign | not specified | 2017-10-27 | 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 | RCV000131679 | SCV000186715 | benign | Hereditary cancer-predisposing syndrome | 2014-12-16 | 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. |
Counsyl | RCV000077387 | SCV000221133 | likely benign | Breast-ovarian cancer, familial 2 | 2015-02-12 | criteria provided, single submitter | literature only | |
Prevention |
RCV000074551 | SCV000301768 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Institute for Biomarker Research, |
RCV000131679 | SCV000679722 | likely benign | Hereditary cancer-predisposing syndrome | 2017-07-12 | criteria provided, single submitter | clinical testing | |
Color | RCV000131679 | SCV000683816 | benign | Hereditary cancer-predisposing syndrome | 2015-04-07 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000077387 | SCV001268134 | likely benign | Breast-ovarian cancer, familial 2 | 2018-01-13 | 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. |
Illumina Clinical Services Laboratory, |
RCV001110669 | SCV001268135 | uncertain significance | Fanconi anemia, complementation group D1 | 2018-01-13 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Ce |
RCV001200387 | SCV001371332 | likely benign | not provided | 2020-05-01 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000077387 | SCV000109184 | benign | Breast-ovarian cancer, familial 2 | 2012-05-01 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077387 | SCV000146944 | uncertain significance | Breast-ovarian cancer, familial 2 | 2004-02-20 | no assertion criteria provided | clinical testing | |
Department of Medical Genetics, |
RCV000077387 | SCV000301451 | likely benign | Breast-ovarian cancer, familial 2 | 2016-05-01 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001270288 | SCV000592077 | likely benign | breast cancer | no assertion criteria provided | clinical testing | The BRCA2 p.Gly2274Val variant was identified in 8 of 7752 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer and was present in 1 of 2986 control chromosomes (frequency: 0.0003) from healthy individuals (Wagner 1999, Chenevix-Trench 2006, Borg 2010, Morgan 2010, Tamboom 2010, Capanu 2011, Jarhelle 2016, Konecny 2011). The variant was identified in dbSNP (rs55712212) as 'Auwith other allele'Au, ClinVar (classified as likely benign by GeneDx, Counsyl, PreventionGenetics and 4 other submitters; as benign by Color, Invitae, Ambry Genetics and SCRP; and as uncertain significance by BIC, Illumina and 2 other submitters ), LOVD 3.0 (observed 25x) and UMD-LSDB (observed 5x). The variant was identified in control databases in 445 of 267,156 chromosomes (2 homozygous) at a frequency of 0.002, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Finnish in 331 of 25,104 chromosomes (freq: 0.01), Other in 9 of 6654 chromosomes (freq: 0.001), European in 104 of 117,702 chromosomes (freq: 0.0008), and Latino in 1 of 35,100 chromosomes (freq: 0.00003); it was not observed in the African, Ashkenazi Jewish, East Asian or South Asian populations. In multiple studies using multifactorial probability models, likelihood ratios predicted the variant to be 'Auneutral'Au (Chenevix-Trench 2006, Lindor 2012). The p.Gly2274 residue is not 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 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, 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 likely benign. | |
True Health Diagnostics | RCV000131679 | SCV000787943 | likely benign | Hereditary cancer-predisposing syndrome | 2017-08-09 | no assertion criteria provided | clinical testing | |
Foulkes Cancer Genetics LDI, |
RCV000735591 | SCV000863729 | uncertain significance | Breast and/or ovarian cancer | 2014-02-24 | no assertion criteria provided | clinical testing |