Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV003327706 | SCV004034236 | uncertain significance | Warburg micro syndrome 1 | 2023-08-24 | criteria provided, single submitter | research | A heterozygous deletion of exons 20-23 in RAB3GAP1 (NM_012233.3) was identified by exome sequencing in one individual with Warburg micro syndrome, confirmed in trans with a likely pathogenic variant (p.Leu798ArgfsTer7) ([GRCh 38] chr2:135162318_135164794x1). The presence of this deletion was validated by ddPCR. These breakpoints have been estimated by exome sequencing only and therefore may not reflect the true breakpoints. Inheritance information is unavailable. The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. This intragenic deletion of 4 exons is not predicted to alter the protein reading-frame and it is unclear if this deletion will impact the protein. Loss of function of RAB3GAP1 is an established disease mechanism in autosomal recessive Warburg micro syndrome (https://search.clinicalgenome.org/kb/gene-dosage). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.45 points, 3: 0 points, 4-5: 0.30 points; Total: 0.75 points; Riggs 2020 (PMID: 31690835). |