Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000279878 | SCV000469186 | uncertain significance | GLI3-Related Disorders | 2017-04-28 | criteria provided, single submitter | clinical testing | The GLI3 c.2741delG (p.Gly914AlafsTer38) variant causes a frameshift and is predicted to result in a premature termination of the protein. The p.Gly914AlafsTer38 variant has been reported in one study, where it was found in a heterozygous state in an individual with Greig cephalopolysyndactyly who manifested postaxial polydactyly with macrocephaly and hypertelorism and had a family history of preaxial polydactyly (Johnston et al. 2010). A related affected individual was also heterozygous for the p.Gly914AlafsTer38 variant. Control data are unavailable for this variant, and it is not found in the 1000 Genomes Project, the Exome Sequencing Project or the Exome Aggregation Consortium despite being located in a region of good sequencing coverage, suggesting that this is a rare variant. Due to the potential impact of frameshift variants and the available evidence, the p.Gly914AlafsTer38 variant is classified as a variant of unknown significance but is suspicious for pathogenicity for GLI3-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |