Submissions for variant NM_001002295.2(GATA3):c.790T>A (p.Cys264Ser)

dbSNP: rs767074039

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001251506	SCV001427152	pathogenic	Hypoparathyroidism, deafness, renal disease syndrome	2018-12-27	criteria provided, single submitter	clinical testing	A heterozygous missense variant, NM_001002295.1(GATA3):c.790T>A, has been identified in exon 4 of 6 of the GATA3 gene. The variant is predicted to result in a major amino acid change from cysteine to serine at position 264 of the protein (NP_001002295.1(GATA3):p.(Cys264Ser)). The cysteine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the zinc finger domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD). An alternative residue change has been reported in the gnomAD database at a frequency of 0.0004%. This variant has not been previously reported in clinical cases. A different variant in the same codon resulting in a change to arginine has been classified as likely pathogenic (ClinVar). Subsequent analysis of parental samples indicated this variant to be de novo. Based on the information available at the time of curation, this variant has been classified as PATHOGENIC. NB: This variant has been reclassified as pathogenic due to de novo status.