Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001265727 | SCV001443896 | pathogenic | Inborn genetic diseases | 2021-11-09 | criteria provided, single submitter | clinical testing | The c.2810G>A (p.R937H) alteration is located in exon 19 (coding exon 18) of the SMARCA2 gene. This alteration results from a G to A substitution at nucleotide position 2810, causing the arginine (R) at amino acid position 937 to be replaced by a histidine (H). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). The c.2810G>A (p.R937H) alteration was reported de novo in a patient who presented with severe developmental delay and intellectual disability, blepharophimosis, hypotonia, postnatal growth delay, vision problems, and dysmorphic features but lacking the common facial gestalt of Nicolaides-Baraitser syndrome (Cappuccio, 2020). Additionally, this alteration has been reported de novo once from a cohort of patients with intellectual disability (Lelieveld, 2016). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). Based on internal structural analysis, R937H is negligibly destabilizing to the linker between helicase domains in SMARCA2, in a region with no internally classified variants (Liu, 2017; Xia, 2016). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. |
| Baylor Genetics | RCV001330804 | SCV001522621 | likely pathogenic | Nicolaides-Baraitser syndrome | 2020-02-17 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Baylor Genetics | RCV001533104 | SCV001748924 | likely pathogenic | SMARCA2-related BAFopathy | 2021-06-10 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001568826 | SCV001792764 | pathogenic | not provided | 2022-02-18 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32694869) |
| Fondazione Telethon, |
RCV001027662 | SCV001169160 | likely pathogenic | Intellectual disability | no assertion criteria provided | clinical testing |