Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000132216 | SCV000187298 | likely benign | Hereditary cancer-predisposing syndrome | 2019-02-27 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence;In silico models in agreement (benign);Subpopulation frequency in support of benign classification |
Invitae | RCV000203848 | SCV000261976 | likely benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000353391 | SCV000383748 | 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. |
Illumina Clinical Services Laboratory, |
RCV000410842 | SCV000383749 | 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. |
Counsyl | RCV000410842 | SCV000488288 | uncertain significance | Breast-ovarian cancer, familial 2 | 2016-02-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000479638 | SCV000571484 | likely benign | not specified | 2017-11-21 | 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. |
Color | RCV000132216 | SCV000910979 | likely benign | Hereditary cancer-predisposing syndrome | 2016-11-04 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000479638 | SCV000918806 | likely benign | not specified | 2018-01-29 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.6886A>C (p.Ile2296Leu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function and the variant is located outside of any known domain or repeat. The observed variant frequency within South Asian control individuals in the gnomAD database (42/30676 chrs) is approximately 1.87 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00075), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.6886A>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant as VUS/Likely Benign. Based on the evidence outlined above, the variant was classified as likely benign. |
True Health Diagnostics | RCV000132216 | SCV000787946 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-02-05 | no assertion criteria provided | clinical testing |