Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV002789977 | SCV003761257 | likely pathogenic | Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome | 2023-01-25 | criteria provided, single submitter | curation | The heterozygous p.Phe836LeufsTer18 variant in POGZ was identified by our study in one individual with White-Sutton syndrome. Trio exome analysis revealed this variant to be de novo. The p.Phe836LeufsTer18 variant in POGZ has not been previously reported in individuals with White-Sutton syndrome. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 836 and leads to a premature termination codon 18 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the POGZ gene is strongly associated to White-Sutton syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant White-Sutton syndrome. ACMG/AMP Criteria applied: PVS1_Strong, PS2_Moderate, PM2_Supporting (Richards 2015). |