Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000266986 | SCV000330668 | pathogenic | not provided | 2023-08-16 | criteria provided, single submitter | clinical testing | Reported as a heterozygous pathogenic variant in one individual from a cohort of patients with hypotonia; detailed clinical information unavailable (Sharma et al., 2021); Nonsense variant predicted to result in protein truncation, as the last 348 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34480364) |
| Center for Pediatric Genomic Medicine, |
RCV000266986 | SCV000511643 | pathogenic | not provided | 2016-07-06 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV001807206 | SCV002054293 | pathogenic | Coffin-Siris syndrome 1 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Broad Center for Mendelian Genomics, |
RCV001807206 | SCV003922235 | likely pathogenic | Coffin-Siris syndrome 1 | 2023-05-02 | criteria provided, single submitter | curation | The heterozygous p.Lys1902Ter variant in ARID1B was identified by our study in one individual with agenesis of corpus callosum. Trio exome analysis showed this variant to be de novo. The p.Lys1902Ter variant in ARID1B has been previously reported in one individual with Coffin-Siris syndrome 1 (PMID: 34480364). This variant was found to be de novo in one individual with confirmed paternity and maternity (ClinVar Accession ID: SCV000511643.1). This variant has also been reported in ClinVar (Variation ID: 280727) and has been interpreted as pathogenic by GeneDx, Children's Mercy Hospital and Clinics Center for Pediatric Genomic Medicine, and Genome-Nilou Lab. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1902 and leads to a premature termination codon 1 amino acids downstream. This termination codon occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Heterozygous loss of function of the ARID1B gene is an established disease mechanism in autosomal dominant Coffin-Siris syndrome 1. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant Coffin-Siris syndrome 1. ACMG/AMP Criteria applied: PVS1_Strong, PS2_Moderate, PS4_Supporting, PM2_Supporting (Richards 2015). |