ClinVar Miner

Submissions for variant NM_001202.6(BMP4):c.677G>A (p.Arg226Gln)

gnomAD frequency: 0.00004  dbSNP: rs538330477
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001557970 SCV001779826 likely benign not provided 2019-05-16 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31063268)
Invitae RCV002569000 SCV003450482 uncertain significance Microphthalmia with brain and digit anomalies; Orofacial cleft 11 2022-06-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 226 of the BMP4 protein (p.Arg226Gln). This variant is present in population databases (rs538330477, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with BMP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1195040). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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