Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001772568 | SCV001993126 | uncertain significance | not provided | 2019-08-13 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Prevention |
RCV003407792 | SCV004109418 | likely pathogenic | BMP4-related disorder | 2023-06-05 | criteria provided, single submitter | clinical testing | The BMP4 c.928C>T variant is predicted to result in the amino acid substitution p.Arg310Cys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. De novo variants have been reported in individuals with BMP4-related disorders (Tenenbaum-Rakover. 2021. PubMed ID: 34009138; Rodríguez-Contreras. 2019. PubMed ID: 31120642; Blackburn. 2019. PubMed ID: 31053785). This variant is interpreted as likely pathogenic. |
Invitae | RCV003771968 | SCV004595004 | uncertain significance | Microphthalmia with brain and digit anomalies; Orofacial cleft 11 | 2023-04-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1307713). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BMP4 protein function. This variant has not been reported in the literature in individuals affected with BMP4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 310 of the BMP4 protein (p.Arg310Cys). |