Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000569082 | SCV000666241 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-09-13 | criteria provided, single submitter | clinical testing | The c.2493-5dupT intronic variant, results from a duplication of two nucleotides at nucleotide position 2493 before intron 16 of the BRIP1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001087685 | SCV001131787 | benign | Familial cancer of breast; Fanconi anemia complementation group J | 2023-09-08 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000983761 | SCV001134016 | uncertain significance | not provided | 2019-03-15 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000569082 | SCV001347923 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001584378 | SCV001821423 | uncertain significance | not specified | 2021-08-29 | criteria provided, single submitter | clinical testing | Variant summary: BRIP1 c.2493-5dupT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 4e-06 in 250958 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2493-5dupT in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (Benign, n=1; VUS, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance. |