DDG2P
Gene: FMR1
The DDG2P confidence category for the disease FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623 is definitive. The allelic requirement, mutation consequence and cross cutting modifier are monoallelic_X_hem, altered gene product structure and potential IF respectively.
The DDG2P confidence category for the disease PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360 is definitive. The allelic requirement, mutation consequence and cross cutting modifier are monoallelic_X_het, uncertain and potential IF respectively.
The DDG2P confidence category for the disease FRAGILE X SYNDROME, OMIM:300624 is definitive. The allelic requirement and mutation consequence are monoallelic_X_hem and absent gene product.Created: 4 Oct 2023, 5:08 p.m. | Last Modified: 6 Oct 2023, 11:17 a.m.
Panel Version: 3.15
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360; FRAGILE X SYNDROME, OMIM:300624
September 2019: G2P confidence terminology was updated: DD-G2P rating is now 'both RD and IF' for FRAGILE X TREMOR/ATAXIA SYNDROME; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1.Created: 8 Oct 2019, 3:24 p.m. | Last Modified: 8 Oct 2019, 3:24 p.m.
Panel Version: 1.131
Changed rating from Amber to Green: agreed by the Genomics England clinical team that the DDG2P Disease confidence of 'both DD and IF' should be represented by a Green rating in PanelApp. FMR1 also rated 'confirmed' for FRAGILE X SYNDROME.Created: 12 Jul 2019, 9:15 p.m. | Last Modified: 12 Jul 2019, 9:15 p.m.
Panel Version: 1.76
Comment on mode of inheritance: DDG2P mode of inheritance is hemizygous for FRAGILE X SYNDROME (confirmed); hemizygous for FRAGILE X TREMOR/ATAXIA SYNDROME (both DD and IF); x-linked dominant for PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 (both DD and IF).Created: 11 Jun 2019, 8:33 p.m.
Changed rating to Amber to reflect DDG2P Disease confidence of 'both DD and IF' for FRAGILE X TREMOR/ATAXIA SYNDROME; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1. FMR1 also rated 'confirmed' for FRAGILE X SYNDROME.Created: 29 Jan 2019, 12:14 p.m.
Multiple MOPs in DD-G2P download: activating, loss of function, uncertain. Multiple MOIs in DD-G2P download: hemizygous and x-linked dominant. Multiple ratings in DD-G2P download: Rated both DD and IF for FRAGILE X TREMOR/ATAXIA SYNDROME 300623 and PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 311360. Rated confirmed for FRAGILE X SYNDROME 300624.Created: 19 Nov 2018, 11:29 a.m.
Phenotypes for gene: FMR1 were changed from FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360; FRAGILE X SYNDROME, OMIM:300624 to FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360; FRAGILE X SYNDROME, OMIM:300624
Phenotypes for gene: FMR1 were changed from FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360; FRAGILE X SYNDROME, OMIM:300624 to FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360; FRAGILE X SYNDROME, OMIM:300624
Phenotypes for gene: FMR1 were changed from FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360; FRAGILE X SYNDROME, OMIM:300624 to FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360; FRAGILE X SYNDROME, OMIM:300624
Phenotypes for gene: FMR1 were changed from PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 311360; FRAGILE X SYNDROME 300624; FRAGILE X TREMOR/ATAXIA SYNDROME 300623 to FRAGILE X TREMOR/ATAXIA SYNDROME, OMIM:300623; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1, OMIM:311360; FRAGILE X SYNDROME, OMIM:300624
Source Expert Review Green was added to FMR1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mode of inheritance for gene: FMR1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rebecca Foulger: Multiple MOPs in DD-G2P downlo
Source Expert Review Amber was added to FMR1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Added phenotypes PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 311360 for gene: FMR1
Added phenotypes FRAGILE X SYNDROME 300624 for gene: FMR1
gene: FMR1 was added gene: FMR1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: FMR1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: FMR1 were set to FRAGILE X TREMOR/ATAXIA SYNDROME 300623