Submissions for variant NM_001211.6(BUB1B):c.464A>G (p.Tyr155Cys)

gnomAD frequency: 0.00006  dbSNP: rs764923350

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002240154	SCV001206747	uncertain significance	Mosaic variegated aneuploidy syndrome 1	2024-12-08	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 155 of the BUB1B protein (p.Tyr155Cys). This variant is present in population databases (rs764923350, gnomAD 0.009%). This missense change has been observed in individual(s) with mosaic variegated aneuploidy, kidney cancer (PMID: 20516114, 34308104). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 840920). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BUB1B function (PMID: 20516114). 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003238280	SCV002010624	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005012475	SCV005638060	uncertain significance	Mosaic variegated aneuploidy syndrome 1; Premature chromatid separation trait; Colorectal cancer	2024-01-03	criteria provided, single submitter	clinical testing