Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5
The NM_001904.4(CTNNB1):c.101G>A(p.Gly34Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic,other (no stars).
CTNNB1 (HGNC:2514): (catenin beta 1) The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the CTNNB1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 43 curated pathogenic missense variants (we use a threshold of 10). The gene has 15 curated benign missense variants. Gene score misZ: 3.846 (above the threshold of 3.09). Trascript score misZ: 5.712 (above the threshold of 3.09). GenCC associations: The gene is linked to severe intellectual disability-progressive spastic diplegia syndrome, exudative vitreoretinopathy, exudative vitreoretinopathy 7.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.829
PP5
Variant 3-41224613-G-A is Pathogenic according to our data. Variant chr3-41224613-G-A is described in ClinVar as [Pathogenic, other]. Clinvar id is 17584.Status of the report is no_assertion_criteria_provided, 0 stars.
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