Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV003327638 | SCV004034174 | pathogenic | Rett syndrome, congenital variant | 2023-08-24 | criteria provided, single submitter | research | A confirmed de novo heterozygous deletion of 2 genes was identified by exome sequencing in one individual with Rett syndrome ([GRCh 38] chr14:28766690_29666306x1). These breakpoints have been estimated by exome sequencing only and therefore may not reflect the true breakpoints. The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. There is complete overlap with the FOXG1 gene, which is known to be haploinsufficient and has been assessed by the ClinGen Dosage Sensitivity Working Group (https://search.clinicalgenome.org/kb/gene-dosage). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Rett syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 1 points, 3: 0 points, 4-5: 0.15 points Total: 1.15 points; Riggs 2020 (PMID: 31690835). |