Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001089562 | SCV001244772 | pathogenic | Hypoparathyroidism, deafness, renal disease syndrome | 2017-09-25 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_001002295.1(GATA3):c.961T>A in exon 5 of the GATA3 gene.This substitution is predicted to create a major amino acid change from a cysteine to a serine at position 321, NP_001002295.1(GATA3):p.(Cys321Ser).The cysteine at this position has very high conservation (100 vertebrates, UCSC). In silico tools predict this variant to be deleterious (Polyphen, SIFT, CADD, Mutation Taster).This variant is not present in the gnomAD population database. A variant affecting the same amino acid has been previously reported in a patient with hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome (Ohta, M. et al. (2011).)It is located in the C-terminal zinc finger (ZnF2) DNA-binding domain that has four cysteine residues. Functional studies have shown that disrupting this cysteine causes loss of DNA-binding (Ohta, M. et al. (2011)). Parental testing has indicated the variant is due to a de novo event.Based on current information, this variant has been classified asPATHOGENIC.NB: The GATA3 variant has been reclassified to pathogenic due to de novo status. |