Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000007162 | SCV001397433 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2023-07-08 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with mosaic variegated aneuploidy (PMID: 15475955, 18548531). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects BUB1B function (PMID: 20516114, 31738183). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 6765). This variant is present in population databases (rs28989185, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1012 of the BUB1B protein (p.Leu1012Pro). |
Fulgent Genetics, |
RCV002482838 | SCV002787995 | uncertain significance | Mosaic variegated aneuploidy syndrome 1; Premature chromatid separation trait; Colorectal cancer | 2022-03-21 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509147 | SCV002819709 | uncertain significance | not specified | 2022-12-21 | criteria provided, single submitter | clinical testing | Variant summary: BUB1B c.3035T>C (p.Leu1012Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251458 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3035T>C has been reported in the literature as a compound heterozygous genotype with another loss of function variant in at-least one individual affected with features of recessive Mosaic Variegated Aneuploidy Syndrome (Hanks_2004). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect as presented although a decrease in protein abundance was reported (Suijkerbuijk_2010). Recently, an animal mouse model of the human genotype mentioned above demonstrated that mice modeling MVA patient BUBR1X753/L1012P die during early embryogenesis (Sieben_2020). The authors conclude that a mouse model for MVA patient BUBR1X753/L1012P is unattainable, most likely due to severe mitotic defects that interfere with early embryogenesis. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
OMIM | RCV000007162 | SCV000027358 | pathogenic | Mosaic variegated aneuploidy syndrome 1 | 2004-11-01 | no assertion criteria provided | literature only | |
OMIM | RCV000007163 | SCV000027359 | affects | Premature chromatid separation trait | 2004-11-01 | no assertion criteria provided | literature only |