ClinVar Miner

Submissions for variant NM_001211.6(BUB1B):c.2762A>T (p.Gln921Leu)

gnomAD frequency: 0.00015  dbSNP: rs141119531
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002233433 SCV000835294 uncertain significance Mosaic variegated aneuploidy syndrome 1 2022-07-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 582237). This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. This variant is present in population databases (rs141119531, gnomAD 0.04%). This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 921 of the BUB1B protein (p.Gln921Leu).
Ambry Genetics RCV002440543 SCV002750344 uncertain significance Inborn genetic diseases 2025-01-20 criteria provided, single submitter clinical testing The c.2762A>T (p.Q921L) alteration is located in exon 21 (coding exon 21) of the BUB1B gene. This alteration results from a A to T substitution at nucleotide position 2762, causing the glutamine (Q) at amino acid position 921 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002233433 SCV005402415 uncertain significance Mosaic variegated aneuploidy syndrome 1 2024-01-20 criteria provided, single submitter clinical testing The BUB1B c.2762A>T (p.Gln921Leu) missense change has a maximum subpopulation frequency of 0.04% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with mosaic variegated aneuploidy syndrome. In summary, the evidence currently available is insufficient to determine the role of this variant in mosaic variegated aneuploidy syndrome. It has therefore been classified as of uncertain significance.

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