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| Undiagnosed metabolic disorders v1.527 | OPA1 | Arina Puzriakova Phenotypes for gene: OPA1 were changed from Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Optic atrophy 1, 165500; {Glaucoma, normal tension, susceptibility to}, 606657; Optic atrophy plus syndrome, 125250; Mitochondrial DNA Depletion Syndrome; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions to Optic atrophy 1, OMIM:165500; Optic atrophy plus syndrome, OMIM:125250; Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type), OMIM:616896; Behr syndrome, OMIM:210000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.440 | GLS |
Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber. There are sufficient cases, supported by functional data, to rate this gene Green - however, detection of the 5' UTR triplet expansion (PMID:30970188) must first be validated within the Genomics England pipeline. When excluding cases with the STR, the remaining evidence is not sufficient for inclusion as diagnostic-grade and therefore keeping Amber until the STR is validated or additional cases arise. |
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| Undiagnosed metabolic disorders v1.365 | ISCA2 |
Sarah Leigh gene: ISCA2 was added gene: ISCA2 was added to Undiagnosed metabolic disorders. Sources: Literature Mode of inheritance for gene: ISCA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ISCA2 were set to 25539947; 29359243 Phenotypes for gene: ISCA2 were set to Multiple mitochondrial dysfunctions syndrome 4 616370 Review for gene: ISCA2 was set to GREEN Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two different ethinicities. Rated green based on review of Anna de Burca (Clinical Fellow, Genomic England). Sources: Literature |
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| Undiagnosed metabolic disorders v1.342 | ATP5A1 | Sarah Leigh changed review comment from: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys in this publication have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys in this publication have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.316 | ATP5A1 | Sarah Leigh changed review comment from: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.; to: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys in this publication have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.247 | ATP5A1 | Sarah Leigh Added comment: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.131 | TANGO2 | Sarah Leigh Added comment: Comment on list classification: Based on recommendations of Helen Britain (Clinical Fellow, Genomics England) as cases will have of periods of decompensation that are associated with hypoglycaemia and hyperammonaemia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.129 | STAT2 | Sarah Leigh Added comment: Comment on list classification: Based on recommendation of Helen Britain (Clinical Fellow, Genomics England), that the majority of cases will be presenting in the context of overwhelming infection. The raised lactate and encephalomyopathy are potentially relevant phenotypes for this panel, however more evidence is needed on how common this presentation is, and whether it is always clearly associated with a proven infection. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.127 | IER3IP1 | Sarah Leigh Added comment: Comment on list classification: Based on recommendation of Helen Britain (Clinical Fellow, Genomics England), that patients will present with features of microcephaly / neonatal diabetes / developmental delay, rather than metabolic disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.121 | RANBP2 | Sarah Leigh Added comment: Comment on list classification: Demoted RANBP2 from Green to Amber following review by Zornitza Stark and agreement from Helen Brittain (Genomics England clinical team). Recent papers report patients with symptoms (including seizures) after a viral illness (PMID:30796099, PMID:28336122, PMID:25128471). However, listed as a susceptibility locus in OMIM, and papers report incomplete penetrance: variant present in asymptomatic maternal grandmother in PMID:30796099 and in the father in PMID:28336122. Therefore further information (e.g. on penetrance) is required for a clear gene:disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.117 | FUT8 |
Louise Daugherty gene: FUT8 was added gene: FUT8 was added to Undiagnosed metabolic disorders. Sources: Expert Review Mode of inheritance for gene: FUT8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FUT8 were set to 29304374 Phenotypes for gene: FUT8 were set to Congenital disorder of glycosylation with defective fucosylation, 618005 Review for gene: FUT8 was set to GREEN Added comment: Adding to Undiagnosed metabolic disorders panel after reviewing panels for GMS, as recommended by the Genomics England clinical team, to benefit the 100K participants. Enough evidence to support gene-disease association and relevance to this panel to rate this gene Green. Sources: Expert Review |
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