Activity
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| Intellectual disability v5.268 | U2AF2 |
Celia Duff-Farrier changed review comment from: Literature evidence Ref1-5, identification of affected patients in the diagnostic setting (CVA database, 19:55661148:C>T ) and further accounts in open access databases (ClinVar and LOVD), make this gene suitable for clinical review and upgrading to a green gene status on relevant panels. It is associated with a phenotype encompassing dysmorphism, epilepsy, developmental delay, intellectual disability, and brain malformation Ref1-5. There is a recent publication that proposes an extension of this phenotype to include hypomyelination leukodystrophy Ref6. A loss of function mechanism has been suggested, associated with disruption of RNA recognition motifs required for the function of U2AF2 as a pre-mRNA splicing factor Ref4. At least one recurrent pathogenic variant has been identified by this review U2AF2 c.445C>T p.(Arg149Trp). U2AF2 is constrained for missense in gnomAD Z=4.71. total variants reported 1) De novo U2AF2 (NM_007279.3:c.445C>T p.(Arg149Trp)) recurrent variant; 1x patient in Hiraide (PubMed: 34112922), 1x patient in Kittock (PubMed: 37092751), 2x patients in Kaplanis (Pubmed: 33057194), 7x patients in the Leiden Open Variation Database (LOVD, https://www.lovd.nl/), 1x patient in house BGL and 4x additional on CVA 2) De novo U2AF2 c.603G>T; 1 patient in Wang 2023 (PubMed: 36747105) 3) De novo U2AF2 c.470C>T p.Pro157Leu) in Kuroda (PubMed: 37134193) 4) 9x additional pathogenic or likely pathogenic variants on LOVD 5) 2x additional likely pathogenic variants on ClinVar References 1. PubMed: 28135719 McRae (2017)-DDD data 2. PubMed: 31785789 Turner (2019)-DDD data 3. PubMed: 34112922 Hiraide (2021) de novo U2AF2 c.445C>T p.R149W 4. PubMed: 36747105 Wang (2023) de novo U2AF2 c.603G>T, p.163_201del 5. PubMed: 37092751 Kittock (2023) de novo U2AF2 c.445C>T p.R149W Possible emerging phenotype of hypomyelinating leukodystrophy 6. PubMed: 37134193 Kuroda (2023); to: Literature evidence Ref1-5, identification of affected patients in the diagnostic setting (CVA database, 19:55661148:C>T ) and further accounts in open access databases (ClinVar and LOVD), make this gene suitable for clinical review and upgrading to a green gene status on relevant panels. It is associated with a phenotype encompassing dysmorphism, epilepsy, developmental delay, intellectual disability, and brain malformation Ref1-5. There is a recent publication that proposes an extension of this phenotype to include hypomyelination leukodystrophy Ref6. A loss of function mechanism has been suggested, associated with disruption of RNA recognition motifs required for the function of U2AF2 as a pre-mRNA splicing factor Ref4. At least one recurrent pathogenic variant has been identified by this review U2AF2 c.445C>T p.(Arg149Trp). U2AF2 is constrained for missense in gnomAD Z=4.71. total variants/patients identified 1) De novo U2AF2 (NM_007279.3:c.445C>T p.(Arg149Trp)) recurrent variant; 1x patient in Hiraide (PubMed: 34112922), 1x patient in Kittock (PubMed: 37092751), 2x patients in Kaplanis (Pubmed: 33057194), 7x patients in the Leiden Open Variation Database (LOVD, https://www.lovd.nl/), 1x patient in house BGL and 4x additional on CVA 2) De novo U2AF2 c.603G>T; 1 patient in Wang 2023 (PubMed: 36747105) 3) De novo U2AF2 c.470C>T p.Pro157Leu) in Kuroda (PubMed: 37134193) 4) 9x additional pathogenic or likely pathogenic variants on LOVD 5) 2x additional likely pathogenic variants on ClinVar 6) We are collaborating with a researcher in the USA with a cohort of 40+ cases. References 1. PubMed: 28135719 McRae (2017)-DDD data 2. PubMed: 31785789 Turner (2019)-DDD data 3. PubMed: 34112922 Hiraide (2021) de novo U2AF2 c.445C>T p.R149W 4. PubMed: 36747105 Wang (2023) de novo U2AF2 c.603G>T, p.163_201del 5. PubMed: 37092751 Kittock (2023) de novo U2AF2 c.445C>T p.R149W Possible emerging phenotype of hypomyelinating leukodystrophy 6. PubMed: 37134193 Kuroda (2023) |
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| Intellectual disability v3.421 | KIT |
Arina Puzriakova Source Expert Review Red was added to KIT. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
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| Intellectual disability v3.253 | KIT | Arina Puzriakova commented on gene: KIT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.0 | KIT | Zornitza Stark reviewed gene: KIT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.821 | TRAF7 | Rebecca Foulger Added comment: Comment on list classification: TRAF7 was added to the panel and rated Green by Konstantinos Varvagiannis based on PMID:29961569 (Tokita et al, 2018) who report four different heterozygous missense mutations in the TRAF7 gene in 7 unrelated patients with MIM:618164. The variants were de novo in at least six of the patients. Motor and/or speech delay were present to a variable degree in 5 of the 5 subjects for whom this outcome could be assessed (The remaining two subjects were 1 week old and 3 weeks old). After discussion with Louise Daugherty, I have rated TRAF7 as Amber: PMID:29961569 assayed motor delay and speech delay as indicators of developmental delay- the authors don't refer to global DD, and motor/speech delay are not directly linked to ID. Additional evidence comes from an ID cohort study (PMID:27479843, Lelieveld et al, 2016) and the DDD study (PMID:28135719). Rated Amber with a 'watchlist' tag, awaiting further evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.398 | ISCA-37432-Loss |
Louise Daugherty Region: ISCA-37432-Loss was added Region: ISCA-37432-Loss was added to Intellectual disability. Sources: ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37432-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for Region: ISCA-37432-Loss were set to RCAD syndrome; utero-vaginal atresia; Schizophrenia; 614527; delayed development, intellectual disability; Renal cysts and diabetes syndrome; Autism Spectrum Disorder; Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome in females; Chromosome 17q12 deletion syndrome; global developmental delay |
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| Intellectual disability | KIT | BRIDGE consortium edited their review of KIT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | KIT | Louise Daugherty classified KIT as amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | KIT | Louise Daugherty commented on KIT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | KIT | BRIDGE consortium reviewed KIT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||