Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002231798 | SCV000640404 | uncertain significance | Mosaic variegated aneuploidy syndrome 1 | 2024-04-22 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 81 of the BUB1B protein (p.Tyr81Cys). This variant is present in population databases (no rsID available, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 465370). 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. 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. |
St. |
RCV000540478 | SCV002012402 | uncertain significance | Mosaic variegated aneuploidy syndrome | 2021-09-22 | criteria provided, single submitter | clinical testing | The BUB1B c.242A>G (p.Tyr81Cys) missense change has a maximum subpopulation frequency of 0.019% in gnomAD v3.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/variant/15-40170539-A-G?dataset=gnomad_r3). Six of seven in silico tools predict a deleterious effect of this variant on protein function (PP3), but to our knowledge these predictions have not been confirmed by functional assays. This variant was reported in a hepatocellular carcinoma but was not present in the patient's germline (PMID: 22561517). To our knowledge, this variant has not been reported in individuals with mosaic variegated aneuploidy syndrome. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting, PP3. |
Fulgent Genetics, |
RCV002476149 | SCV002791252 | uncertain significance | Mosaic variegated aneuploidy syndrome 1; Premature chromatid separation trait; Colorectal cancer | 2021-09-01 | criteria provided, single submitter | clinical testing |