Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genomic Medicine Lab, |
RCV000754643 | SCV000882573 | pathogenic | Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome | 2018-04-26 | criteria provided, single submitter | clinical testing | A reportable heterozygous frameshift variant in the KAT6A, gene(c.4038delT) was identified at chromosomal position chr8: 41791700 (hg19). The KAT6A gene is a member of the MYST family of proteins. KAT6A is a lysine acetyltransferase and is part of the complex responsible for transcriptional regulation through acetylation of lysine 9 on histone H3. Variants in this gene are associated with Mental Retardation, Autosomal Dominant 32; MRD32 (MIM: 616268). In particular individuals with de novo loss of function variants in this gene have been described to have global developmental delay with speech delay, microcephaly, hypotonia, feeding difficulties, and subtle facial dysmorphysm including thin upper lip, bitemporal narrowing / large forehead, flat nasal bridge with broad nasal tip, microretrognathia and posteriorly located or low-set years. Congenital cardiac defects, ocular abnormalities and cardiac defects have also been reported while intermitted neutropenia has been described in one patient. This variant is not reported in the 1000 Genomes, ExAC, or gnomAD population sequencing projects and data from the ExAC database show that this gene is intolerant to loss of function variants (pLI=1). Furthermore, this variant is located in the acidic glutamate/aspartate-rich region consistent with the location of other pathogenic truncating variants reported to date. |
| Gene |
RCV001008898 | SCV001168704 | likely pathogenic | not provided | 2018-07-18 | criteria provided, single submitter | clinical testing | The c.4038delT variant in the KAT6A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.4038delT variant causes a frameshift starting with codon Valine 1347, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Val1347PhefsX6. This variant is predicted to cause loss of normal protein function through protein truncation. The c.4038delT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.4038delT as a likely pathogenic variant. |