Adult onset neurodegenerative disorder
Gene: DNAJC7
To date, DNAJC7 variants have not been associated with a phenotype in OMIM, Gen2Phen or Mondo. Numerous DNAJC7 variants have been reported in amyotrophic lateral sclerosis (ALS) patients (PMID: 31768050; 35039179;34233860; 32897108; 37870677; 35456894). ClinGen classifies the gene disease association between DNAJC7 variants and ALS as Limited (27th Oct 2022), because the ALS Gene Curation Expert Panel only scores protein truncating variants in DNAJC7 as part of the gene disease association classification process. In a survey of variants from various international sources, Farhan et al (PMID: 31768050) collated five DNAJC7 truncating variants in ALS patients.Created: 9 Jan 2024, 5:59 p.m. | Last Modified: 9 Jan 2024, 6:13 p.m.
Panel Version: 4.45
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 9 Jan 2024, 5:28 p.m. | Last Modified: 9 Jan 2024, 5:28 p.m.
Panel Version: 4.45
Two cohort studies in ALS patients identified 11 and 1 patient, respectively, with variants in DNAJC7. Seven of these are putative PTVs. No segregation or functional data. A small number of individuals with LOF variants are present in gnomad albeit less than expected. Given these are cohort studies, and an adult-onset condition, potentially of variable penetrance, we have taken a cautious approach and rated Amber for now but would be interested in other expert opinions. No PMID yet.
Sources: LiteratureCreated: 8 Sep 2020, 10:33 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
amyotrophic lateral sclerosis
Publications
Tag Q4_23_promote_green tag was added to gene: DNAJC7.
Gene: dnajc7 has been classified as Amber List (Moderate Evidence).
Publications for gene: DNAJC7 were set to https://doi.org/10.1212/NXG.0000000000000503
Gene: dnajc7 has been classified as Amber List (Moderate Evidence).
gene: DNAJC7 was added gene: DNAJC7 was added to Neurodegenerative disorders - adult onset. Sources: Literature Mode of inheritance for gene: DNAJC7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DNAJC7 were set to https://doi.org/10.1212/NXG.0000000000000503 Phenotypes for gene: DNAJC7 were set to amyotrophic lateral sclerosis Review for gene: DNAJC7 was set to AMBER