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Intellectual disability - microarray and sequencing v3.1514 | CDK19 | Arina Puzriakova Tag for-review was removed from gene: CDK19. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1510 | CDK19 | Sarah Leigh commented on gene: CDK19: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1510 | CDK19 | Sarah Leigh commented on gene: CDK19: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1509 | CDK19 | Arina Puzriakova Source NHS GMS was added to CDK19. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1509 | CDK19 |
Arina Puzriakova Source Expert Review Green was added to CDK19. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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Intellectual disability - microarray and sequencing v3.963 | CDK19 | Sarah Leigh edited their review of gene: CDK19: Added comment: There is enough evidence for this gene to be rated GREEN at the next major review.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.963 | CDK19 |
Julia Baptista changed review comment from: De novo missense variants mapped to the kinase domain of CDK19 were described in 11 unrelated individuals (age range: 9 months to 14 years).Two recurrent changes at residues Tyr32 and Gly28 were identified. One additional case report (PMID:33568421) described a 10-month-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms and a de novo missense variant c.92C>A (p.Thr31Asn) (also in the kinase domain). This brings the total of cases reported in the literature to 15.; to: De novo missense variants mapped to the kinase domain of CDK19 were described in 11 unrelated individuals (age range: 9 months to 14 years).Two recurrent changes at residues Tyr32 and Gly28 were identified. One additional case report (PMID:33568421) described a 10-month-old male patient who presented with a neurodevelopmental syndrome characterized by infantile spasms and a de novo missense variant c.92C>A (p.Thr31Asn) (also in the kinase domain). This brings the total of cases reported in the literature to 15. |
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Intellectual disability - microarray and sequencing v3.963 | CDK19 | Julia Baptista reviewed gene: CDK19: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33495529, 33568421, 32330417; Phenotypes: developmental delay, hypotonia, seizures, autism/autistic traits; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.150 | CDK19 | Sarah Leigh Tag for-review tag was added to gene: CDK19. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.150 | CDK19 | Sarah Leigh Classified gene: CDK19 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.150 | CDK19 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 3 unrelated cases, together with supportive Drosophila, demonstating the effects of the variants (PMID 32330417). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.150 | CDK19 | Sarah Leigh Gene: cdk19 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.149 | CDK19 | Sarah Leigh Phenotypes for gene: CDK19 were changed from microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation to Epileptic encephalopathy, early infantile, 87 618916 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.148 | CDK19 | Sarah Leigh Publications for gene: CDK19 were set to 20563892 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.148 | CDK19 | Sarah Leigh Mode of inheritance for gene: CDK19 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.31 | CDK19 | Zornitza Stark reviewed gene: CDK19: Rating: GREEN; Mode of pathogenicity: None; Publications: 32330417; Phenotypes: Intellectual disability, epileptic encephalopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.787 | CDK8 |
Konstantinos Varvagiannis commented on gene: CDK8: Calpena et al. (2019 - PMID: 30905399 - DDD study among the co-authors) report on 12 unrelated individuals with pathogenic CDK8 missense variants. Common features included hypotonia and DD (universal feature). Older children displayed variable degrees of ID (2 mild, 5 moderate, 2 moderate-severe). Other features included feeding difficulties, behavioral disorders, CHD, epilepsy (2 individuals), impaired vision and hearing problems in few. CDK8 (alternatively CDK19) serves a one of the four subunits of a kinase module that reversibly binds to the mediator complex to regulate its activity (in turn, regulation of transcription). Mutations in other genes coding for the 3 other subunits of the kinase module (eg. MED12 or MED13L) lead to syndromic neurodevelopmental disorders. 8 missense CDK8 variants were reported in total. Ser62Leu (NM_001260.2:c.185C>T) was recurrent, observed in 5 subjects. The variants had occurred as de novo events in all cases (10 individuals) where parental samples were available. All variants clustered in the kinase domain (residues 21-335 - of 464 total) around the ATP binding pocket. A thermal stability assay did not reveal gross protein instability in the presence or absence of ATP while the ability to bind ATP was retained for most/all variants. Study of STAT1 phosphorylation was suggestive of attenuated kinase activity for all variants, though to a lesser degree for 2 of them. Given the type of variants (all missense) and the pLI of 0.38 haploinsufficiency appears to be unlikely. A dominant-negative mechanism is favoured. CDK8 is not associated with any phenotype in G2P. As a result, CDK8 can be considered for upgrade to green or amber (if the degree of ID is relevant for the current panel). |
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Intellectual disability - microarray and sequencing | CDK19 | Ellen McDonagh Added gene to panel |