Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002446411 | SCV002734279 | pathogenic | Inborn genetic diseases | 2017-12-14 | criteria provided, single submitter | clinical testing | The c.2309dupA pathogenic mutation, located in coding exon 14 of the POGZ gene, results from a duplication of A at nucleotide position 2309, causing a translational frameshift with a predicted alternate stop codon (p.Y770*). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Victorian Clinical Genetics Services, |
RCV004785705 | SCV005399019 | pathogenic | Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome | 2024-10-09 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with White-Sutton syndrome (MIM#616364). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many NMD-predictd variants have been reported as pathogenic (ClinVar, DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic once in ClinVar. An alternate nucleotide substitution resulting in the same protein outcome has been reported in the literature in an individual with moderate intellectual disability and an individual with White-Sutton syndrome. In both literature reports the variant was de novo (PMIDs: 33277917, 34645992). SP) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |