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| Intellectual disability - microarray and sequencing v3.1510 | USP7 | Arina Puzriakova Tag for-review was removed from gene: USP7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1510 | USP7 | Sarah Leigh commented on gene: USP7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.1509 | USP7 |
Arina Puzriakova Source Expert Review Green was added to USP7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Intellectual disability - microarray and sequencing v3.454 | USP7 | Arina Puzriakova Publications for gene: USP7 were set to 30679821; 26365382; 19946331 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.453 | USP7 | Arina Puzriakova Phenotypes for gene: USP7 were changed from Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism to Hao-Fountain syndrome, 616863 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.452 | USP7 | Arina Puzriakova Classified gene: USP7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.452 | USP7 | Arina Puzriakova Added comment: Comment on list classification: Based on published evidence and expert reviews, this gene should be promoted from Amber to Green at the next GMS panel update (added 'for-review' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.452 | USP7 | Arina Puzriakova Gene: usp7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.451 | USP7 | Arina Puzriakova Tag for-review tag was added to gene: USP7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.451 | USP7 | Arina Puzriakova reviewed gene: USP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26365382, 30679821, 33012787; Phenotypes: Hao-Fountain syndrome, 616863; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.420 | USP7 | Konstantinos Varvagiannis edited their review of gene: USP7: Changed publications: 26365382, 19946331, 33012787 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.420 | USP7 | Konstantinos Varvagiannis changed review comment from: Please consider also PMID : 33012787 for Green rating (several cases reported).; to: Please consider also PMID : 33012787 for Green rating (several cases reported to date). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.420 | USP7 | Konstantinos Varvagiannis commented on gene: USP7: Please consider also PMID : 33012787 for Green rating (several cases reported). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.170 | TMEM106B |
Konstantinos Varvagiannis gene: TMEM106B was added gene: TMEM106B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TMEM106B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TMEM106B were set to 29186371; 29444210; 32595021 Phenotypes for gene: TMEM106B were set to Leukodystrophy, hypomyelinating, 16 (MIM #617964) Penetrance for gene: TMEM106B were set to Complete Mode of pathogenicity for gene: TMEM106B was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: TMEM106B was set to GREEN Added comment: 6 unrelated individuals with Leukodystrophy, hypomyelinating, 16 (MIM #617964) due to a recurrent TMEM106B variant have been reported to date in the literature (Simons et al 2017 - PMID: 29186371, Yan et al 2018 - PMID: 29444210, Ikemoto et al 2020 - PMID: 32595021). While a 3 y.o. female described by Yan et al had DD (eg sitting at 9m, walking at 25m) with normal cognitive functioning, and a 38 y.o. female had borderline intellectual functioning (IQ 76), 4 affected individuals had ID. Among them, a 19 y.o. male with severe ID was also found to harbor a second de novo possibly damaging USP7 variant. Seizures have been reported in 2 unrelated subjects. [Clinical features are also summarized in table 1 - Ikemoto et al]. All harbored NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) which in almost all cases occurred as a de novo event. In a single case this variant was inherited from a mosaic parent with mild DD in infancy but normal cognition (reported by Simons et al). As discussed by Ito et al (2018 - PMID: 30643851) the encoded protein is a structural component of the lysosomal membrane, playing a role on lysosome acidification. Acidity of the lysosome mediates multiple aspects of lysosomal function. Ito et al, using patient-derived fibroblasts assessed mRNA and protein levels. These were unaltered compared with controls. While TMEM106B had been previously shown to affect lysosome number, morphology and acidification, Ito et al demonstrated increased number of lysosomes in patient cells as well as impaired acidification compared to controls. As commented lysosomes are required for generation of myelin. Recurrence of this missense variant, the presence of pLoF TMEM106B variants in gnomAD as well as the phenotypically normal Tmem106b null mice suggest that this variant may have a gain-of-function or dominant negative effect. Genes for other forms of hypomyelinating lipodystrophy (incl. PLP1) have green rating in the ID panel. Overall TMEM106B can be considered for the ID panel with green rating and the epilepsy panel with amber rating. Sources: Literature |
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| Intellectual disability - microarray and sequencing v3.3 | USP7 | Zornitza Stark reviewed gene: USP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30679821; Phenotypes: ID, Autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.937 | USP7 | Rebecca Foulger Phenotypes for gene: USP7 were changed from to Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.936 | USP7 | Rebecca Foulger Classified gene: USP7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.936 | USP7 | Rebecca Foulger Gene: usp7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.935 | USP7 | Rebecca Foulger Classified gene: USP7 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.935 | USP7 | Rebecca Foulger Added comment: Comment on list classification: USP7 was rated Green by Konstantinos Varvagiannis. Not currently associated with a disorder in OMIM, but has a 'possible' Disease confidence in Gene2Phenotype for the disorder: Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism (based on PMID:26365382). There is now a 2019 paper in addition to PMID:26365382 (PMID:30679821). In total, 22/23 individuals have an ID/DD phenotype, and 23/23 have speech delay. However, the Tyr143Ter variant described by both PMID:26365382 and PMID:30679821 is a VUS, and the microdeletions in other patients cover additional genes (PMID:26365382, Figure 5). Plus three patients in PMID:30679821 harbour variants in additional genes. Therefore although the phenotype is relevant, I have updated the rating from Red to Amber until there is more evidence that USP7 variants are causative. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.935 | USP7 | Rebecca Foulger Gene: usp7 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.934 | USP7 | Rebecca Foulger Mode of inheritance for gene: USP7 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.933 | USP7 |
Rebecca Foulger commented on gene: USP7: PMID:30679821: Fountain et al., 2019 report on the clinical and genetic spectrum of 16 new and 7 previously reported (by PMID:26365382) individuals with USP7 heterozygous de novo variants. The variants include 2 deletions, 3 nonsense, 3 splice site variants and 8 missense variants. Speech delay was seen in 23/23 patients, and ID/DD was seen in 22/23 patients. Note that Patients 18 and 20 harbor additional variants in TMEM106B and SLC2A1, Patient 19 also has a de novo heterozygous 102.5-kb mosaic loss of uncertain significance at 10q21.1. |
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| Intellectual disability - microarray and sequencing v2.933 | USP7 | Rebecca Foulger commented on gene: USP7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.862 | USP7 | Rebecca Foulger Publications for gene: USP7 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.611 | USP7 | Konstantinos Varvagiannis reviewed gene: USP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26365382, 19946331; Phenotypes: Global developmental delay, Delayed speech and language development, Intellectual disability, Behavioral abnormality, Seizures, Abnormality of brain morphology, Hypogonadism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.468 | USP7 |
Louise Daugherty gene: USP7 was added gene: USP7 was added to Intellectual disability. Sources: Victorian Clinical Genetics Services Mode of inheritance for gene: USP7 was set to |
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