Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000164980 | SCV000215673 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-14 | criteria provided, single submitter | clinical testing | Insufficient or conflicting evidence |
Invitae | RCV001085989 | SCV000255149 | likely benign | Familial cancer of breast; Fanconi anemia, complementation group J | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000348888 | SCV000404610 | uncertain significance | Fanconi anemia, complementation group J | 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, 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. |
Gene |
RCV000430204 | SCV000512417 | benign | not specified | 2015-09-21 | 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. |
Genetic Services Laboratory, |
RCV000430204 | SCV000593766 | uncertain significance | not specified | 2016-12-27 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000589721 | SCV000699667 | benign | not provided | 2017-05-08 | criteria provided, single submitter | clinical testing | Variant summary: The BRIP1 c.1474-3T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing, though ESE finder predicts the variant may introduce an SF2/ASF ESE site at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 33 of 120864 control chromosomes from all ethnicities, but was predominantly observed in the South Asian subpopulation at a frequency of 0.001879 (31/16496). This frequency is about 30 times the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625), strongly suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. Multiple clinical diagnostic laboratories have conflicting classifications for this variant including uncertain significance (4x in ClinVar) and benign (1x in ClinVar). The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. |
Counsyl | RCV000662494 | SCV000785013 | uncertain significance | Fanconi anemia, complementation group J; Neoplasm of ovary | 2017-03-14 | criteria provided, single submitter | clinical testing | |
Color | RCV000164980 | SCV000902752 | benign | Hereditary cancer-predisposing syndrome | 2016-11-17 | criteria provided, single submitter | clinical testing |