Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV002221409 | SCV002498669 | uncertain significance | Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome | 2021-10-01 | criteria provided, single submitter | clinical testing | This sequence change in POGZ is predicted to replace threonine with alanine at codon 40 (p.(Thr40Ala)). The threonine residue is moderately conserved (100 vertebrates, UCSC), and is located in a region of moderate missense constraint in no annotated domain (DECIPHER). There is a small physicochemical difference between threonine and alanine. This variant is absent from gnomAD v2.1 and v3.1. To our knowledge, this variant has not been reported in the literature in any individuals with a neurodevelopmental condition. Multiple lines of computational evidence predict a benign effect for the missense substitution (6/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.4.0, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, BP4. |