Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000495454 | SCV000579046 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-06-29 | reviewed by expert panel | curation | Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/). |
Labcorp Genetics |
RCV000122915 | SCV000166173 | benign | Hereditary breast ovarian cancer syndrome | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000162513 | SCV000212905 | likely benign | Hereditary cancer-predisposing syndrome | 2014-10-10 | 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. |
Illumina Laboratory Services, |
RCV000495454 | SCV000383712 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 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, 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. |
Illumina Laboratory Services, |
RCV000329212 | SCV000383713 | 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. |
Color Diagnostics, |
RCV000162513 | SCV000537427 | likely benign | Hereditary cancer-predisposing syndrome | 2015-06-08 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000456829 | SCV000541031 | benign | Familial cancer of breast | 2017-02-23 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001175341 | SCV000694850 | likely benign | not specified | 2019-01-21 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.5268A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 7.2e-05 in 250366 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (7.2e-05 vs 0.00075), allowing no conclusion about variant significance. In addition, the variant was reported in 4/7325 European American women (i.e. with a frequency of 0.000546), who were older than 70 years of age, and never had cancer (in the FLOSSIES database). c.5268A>G has been reported in the literature in a validation study, although with limited information (i.e. lack of co-occurrence and cosegregation data); thus this report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with another pathogenic variant have been reported (BRCA2 c.5946delT/p.Ser1982fsX22 in our internal database), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (3 classifying it as Benign, 2 as Likely Benign, and 1 as a VUS). Based on the evidence outlined above, the variant was classified as likely benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000585978 | SCV000887846 | benign | not provided | 2023-07-31 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000495454 | SCV001526956 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2018-03-22 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Gene |
RCV000585978 | SCV001869823 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000162513 | SCV002536118 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-01 | criteria provided, single submitter | curation | |
Ce |
RCV000585978 | SCV004010220 | likely benign | not provided | 2024-05-01 | criteria provided, single submitter | clinical testing | BRCA2: BP4, BP7 |
True Health Diagnostics | RCV000162513 | SCV000886674 | likely benign | Hereditary cancer-predisposing syndrome | 2018-09-06 | no assertion criteria provided | clinical testing | |
Clinical Genetics Laboratory, |
RCV000585978 | SCV001905959 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000585978 | SCV001959297 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000585978 | SCV001978222 | likely benign | not provided | no assertion criteria provided | clinical testing |