Intellectual disability - microarray and sequencing
Gene: ZNF335 Green List (high evidence)After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changedCreated: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.
Panel Version: 3.1510
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.
Panel Version: 3.1510
Green List (high evidence)
Comment on list classification: There is enough evidence for this gene to be rated Green at the next GMS panel update (added 'for-review' tag).Created: 27 Oct 2020, 11:57 a.m. | Last Modified: 27 Oct 2020, 11:57 a.m.
Panel Version: 3.488
Removed 'watchlist' tag as there are now sufficient cases to support a gene-disease association, and for this gene to be rated Green.Created: 27 Oct 2020, 11:55 a.m. | Last Modified: 27 Oct 2020, 11:55 a.m.
Panel Version: 3.487
At least 6 unrelated families reported in literature with different biallelic variants in ZNF335. Microcephaly is the primary feature of the phenotype, but also in association with intellectual disability in nearly all cases. Only one less severely affected individual (patient B from PMID:29652087), in whom mild delay was also reported.Created: 27 Oct 2020, 11:54 a.m. | Last Modified: 27 Oct 2020, 11:54 a.m.
Panel Version: 3.487
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Microcephaly 10, primary, autosomal recessive, 615095
Publications
Green List (high evidence)
Four unrelated families reported.Created: 4 Mar 2020, 2:11 a.m. | Last Modified: 4 Mar 2020, 2:11 a.m.
Panel Version: 3.3
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Microcephaly 10, primary, autosomal recessive, OMIM #615095
Publications
I don't know
At time of curation, currently Amber on 'Primary Microcephaly - Microcephalic Dwarfism Spectrum' panel as variants identified in 1 family only (PMID:23178126). 2 further related 'Pathogenic' variants submitted to ClinVar by Baylor. And 1 futher 'likely pathogenic' variant submitted to ClinVar by Chicago lab. Correspondance with the labs when curating the microcephaly panel confirmed that both patient phenotypes included DD, and the Baylor patient had recorded ID. Therefore rated as Amber until these (or additional) studies are published.Created: 29 Nov 2017, 11:19 a.m.
Comment on list classification: Kept rating as Red until further variant information becomes available/published.Created: 3 Mar 2017, 1:40 p.m.
2 'Pathogenic' variants submitted to ClinVar by Baylor, under 'Primary autosomal recessive microcephaly 10': NM_022095.3(ZNF335):c.3787G>T (p.Glu1263Ter) NM_022095.3(ZNF335):c.2744_2747delGTGA (p.Ser915Thrfs). Email correspondance with the Baylor lab revealed that the proband's phenotype was developmental delay, intellectual disability, seizures, hypomyelination, failure to thrive. A paper is currently in press in Genome Medicine.Created: 3 Mar 2017, 1:39 p.m.
1 'likely pathogenic' variant submitted to ClinVar by Chicago lab, under 'Primary autosomal recessive microcephaly 10': NM_022095.3(ZNF335):c.2515_2518dupGCCA (p.Thr840Serfs). In email correspondance, the lab confirmed that they saw this variant in one patient, who was reported to have microcephaly, encephalopathy and developmental delay. The variant was heterozygous, and no second variant was found by either sequencing or deletion/duplication studies.Created: 3 Mar 2017, 1:39 p.m.
Mode of inheritance
Unknown
Phenotypes
?Microcephaly 10, primary, autosomal recessive, 615095; developmental delay; intellectual disability
Publications
Tag for-review was removed from gene: ZNF335.
Source NHS GMS was added to ZNF335.
Source Expert Review Green was added to ZNF335. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: ZNF335 were set to 23178126
Gene: znf335 has been classified as Amber List (Moderate Evidence).
Tag watchlist was removed from gene: ZNF335. Tag for-review tag was added to gene: ZNF335.
Phenotypes for gene: ZNF335 were changed from ?Microcephaly 10, primary, autosomal recessive, 615095; developmental delay; intellectual disability to Microcephaly 10, primary, autosomal recessive, 615095
Mode of inheritance for gene: ZNF335 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
Expert Review Amber was added to ZNF335. Panel: Intellectual disability Publications for gene ZNF335 was set to ['23178126']
This gene has been classified as Red List (Low Evidence).
ZNF335 was created by rfoulger
ZNF335 was added to Intellectual disabilitypanel. Sources: Other
If promoting or demoting a gene, please provide comments to justify a decision to move it.
Genes included in a Genomics England gene panel for a rare disease category (green list) should fit the criteria A-E outlined below.
These guidelines were developed as a combination of the ClinGen DEFINITIVE evidence for a causal role of the gene in the disease(a), and the Developmental Disorder Genotype-Phenotype (DDG2P) CONFIRMED DD Gene evidence level(b) (please see the original references provided below for full details). These help provide a guideline for expert reviewers when assessing whether a gene should be on the green or the red list of a panel.
A. There are plausible disease-causing mutations(i) within, affecting or encompassing an interpretable functional region(ii) of this gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
B. There are plausible disease-causing mutations(i) within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
C. As definitions A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g. known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.
AND
D. Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic setting(iv).
AND
E. No convincing evidence exists or has emerged that contradicts the role of the gene in the specified phenotype.
(i)Plausible disease-causing mutations: Recurrent de novo mutations convincingly affecting gene function. Rare, fully-penetrant mutations - relevant genotype never, or very rarely, seen in controls. (ii) Interpretable functional region: ORF in protein coding genes miRNA stem or loop. (iii) Phenotype: the rare disease category, as described in the eligibility statement. (iv) Intermediate penetrance genes should not be included.
It’s assumed that loss-of-function variants in this gene can cause the disease/phenotype unless an exception to this rule is known. We would like to collect information regarding exceptions. An example exception is the PCSK9 gene, where loss-of-function variants are not relevant for a hypercholesterolemia phenotype as they are associated with increased LDL-cholesterol uptake via LDLR (PMID: 25911073).
If a curated set of known-pathogenic variants is available for this gene-phenotype, please contact us at [email protected]
We classify loss-of-function variants as those with the following Sequence Ontology (SO) terms:
Term descriptions can be found on the PanelApp homepage and Ensembl.
If you are submitting this evaluation on behalf of a clinical laboratory please indicate whether you report variants in this gene as part of your current diagnostic practice by checking the box
Standardised terms were used to represent the gene-disease mode of inheritance, and were mapped to commonly used terms from the different sources. Below each of the terms is described, along with the equivalent commonly-used terms.
A variant on one allele of this gene can cause the disease, and imprinting has not been implicated.
A variant on the paternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on the maternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on one allele of this gene can cause the disease. This is the default used for autosomal dominant mode of inheritance where no knowledge of the imprinting status of the gene required to cause the disease is known. Mapped to the following commonly used terms from different sources: autosomal dominant, dominant, AD, DOMINANT.
A variant on both alleles of this gene is required to cause the disease. Mapped to the following commonly used terms from different sources: autosomal recessive, recessive, AR, RECESSIVE.
The disease can be caused by a variant on one or both alleles of this gene. Mapped to the following commonly used terms from different sources: autosomal recessive or autosomal dominant, recessive or dominant, AR/AD, AD/AR, DOMINANT/RECESSIVE, RECESSIVE/DOMINANT.
A variant on one allele of this gene can cause the disease, however a variant on both alleles of this gene can result in a more severe form of the disease/phenotype.
A variant in this gene can cause the disease in males as they have one X-chromosome allele, whereas a variant on both X-chromosome alleles is required to cause the disease in females. Mapped to the following commonly used term from different sources: X-linked recessive.
A variant in this gene can cause the disease in males as they have one X-chromosome allele. A variant on one allele of this gene may also cause the disease in females, though the disease/phenotype may be less severe and may have a later-onset than is seen in males. X-linked inactivation and mosaicism in different tissues complicate whether a female presents with the disease, and can change over their lifetime. This term is the default setting used for X-linked genes, where it is not known definitately whether females require a variant on each allele of this gene in order to be affected. Mapped to the following commonly used terms from different sources: X-linked dominant, x-linked, X-LINKED, X-linked.
The gene is in the mitochondrial genome and variants within this can cause this disease, maternally inherited. Mapped to the following commonly used term from different sources: Mitochondrial.
Mapped to the following commonly used terms from different sources: Unknown, NA, information not provided.
For example, if the mode of inheritance is digenic, please indicate this in the comments and which other gene is involved.