Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000779221 | SCV000915766 | likely pathogenic | Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency | 2017-07-28 | criteria provided, single submitter | clinical testing | The G6PC3 c.144C>G (p.Tyr48Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. This variant has not been reported in the literature. However, another variant at the same locus, c.144C>A, that results in the same amino acid change (p.Tyr48Ter) has been reported in two studies in a total of two individuals with severe congenital neutropenia, one each in a homozygous state and a compound heterozygous state (Boztug et al. 2009; Notarangelo et al. 2014). The c.144C>A variant was absent from 150 control individuals (Notarangelo et al. 2014). The p.Tyr48Ter variant, from either the c.144C>G or c.144C>A change, is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or the Genome Aggregation Database. Based on the clinical evidence for the c.144C>A variant and the potential impact of stop-gained variants, the c.144C>G (p.Tyr48Ter) variant is classified as likely pathogenic for severe congenital neutropenia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |