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| Mendeliome v1.2840 | YWHAZ | Zornitza Stark Phenotypes for gene: YWHAZ were changed from Intellectual disability, MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092, YWHAZ-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2839 | YWHAZ | Zornitza Stark Publications for gene: YWHAZ were set to 36001342 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2838 | YWHAZ | Zornitza Stark Classified gene: YWHAZ as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2838 | YWHAZ | Zornitza Stark Gene: ywhaz has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2837 | YWHAZ |
Zornitza Stark edited their review of gene: YWHAZ: Added comment: PMID 31024343: 5 individuals with de novo variants in this gene, two had a clinical diagnosis of Rasopathy. 3 missense variants and 2 high impact variants (one is NMD escape). Parentage not confirmed in 3. Two had other possible variants of interest. Used Xenopus to investigate the effect of one of the missense variants, S230W, and demonstrated activation of the Raf-MEK-Erk pathway and embryonic defects when expressed at high levels. Suggests GoF as mechanism. Further de novo missense identified in a large cohort of NDDs, PMID 35143101. PMID 35501409: knockout Zebrafish, altered brain activity and behaviour. PMID 22124272, 26207352: two mouse models also support role in brain development. MODERATE by ClinGen, but note this is mostly driven by experimental data points. Also note there is evidence for both GoF and LoF mechanism, potentially two distinct disorders?; Changed rating: AMBER; Changed publications: 36001342, 31024343, 35143101, 35501409, 22124272, 26207352; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, YWHAZ-related |
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| Mendeliome v1.708 | YWHAZ | Zornitza Stark Marked gene: YWHAZ as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.708 | YWHAZ | Zornitza Stark Gene: ywhaz has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.708 | YWHAZ |
Zornitza Stark gene: YWHAZ was added gene: YWHAZ was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YWHAZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: YWHAZ were set to 36001342 Phenotypes for gene: YWHAZ were set to Intellectual disability, MONDO:0001071 Review for gene: YWHAZ was set to RED Added comment: PMID:36001342 reported one large three-generation family with intellectual disability and global developmental delay, where all affected members were identified with a heterozygous missense variant (c.147A>T/ p.Lys49Asn) in YWHAZ gene. Although there were 10 other rare variants located in 10 genes (ARHGAP4, AGPS, APOL3, CES3, DACT2, ECH1, FAM71E2, KREMEN1, YWHAZ, ZFYVE26) that co-segregated with the ID/GDD phenotype were identified in the family, they were either not present in all affected members or present in unaffected members. In addition, computational modeling and knockdown/ knockin studies with Drosophila also confirmed the role of this YWHAZ variant in intellectual disability. Sources: Literature |
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