ClinVar

Description

A heterozygous deletion of 3 genes (https://genescout.omim.org/) was identified by exome sequencing in one individual with cone-rod retinal dystrophy ([GRCh 38] chr19:47794370_47886413x1)(PMID: 34906470). These breakpoints have been estimated by exome sequencing only and therefore may not reflect the true breakpoints. Inheritance information is unavailable. The presence of this deletion was validated by Sanger sequencing. The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. Two deletions of similar genomic content have been reported in ClinVar (Variation ID: 564581, 830780) and have been interpreted as variants of uncertain significance. There is complete overlap with the CRX gene, which is suspected to be haploinsufficient but has not been assessed by the ClinGen Dosage Sensitivity Working Group. Two reported probands from the literature/internal data with cone rod dystrophy have a LoF variant in CRX. The variants reported are confirmed de novo and the reported phenotypes are nonspecific (PMID: 29555955). 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 points, 3: 0 points, 4-5: 0.45 points; Total: 0.45 points; Riggs 2020 (PMID: 31690835).