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Cytopenia - NOT Fanconi anaemia v4.30 FASLG Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: FASLG.
Cytopenia - NOT Fanconi anaemia v4.30 FAS Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: FAS.
Cytopenia - NOT Fanconi anaemia v4.30 FASLG Achchuthan Shanmugasundram commented on gene: FASLG: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Cytopenia - NOT Fanconi anaemia v4.30 FAS Achchuthan Shanmugasundram commented on gene: FAS: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Cytopenia - NOT Fanconi anaemia v4.29 FASLG Achchuthan Shanmugasundram Source Expert Review Green was added to FASLG.
Source NHS GMS was added to FASLG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v4.29 FAS Achchuthan Shanmugasundram Source Expert Review Green was added to FAS.
Source NHS GMS was added to FAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v4.14 CASP10 Achchuthan Shanmugasundram Added comment: Comment on list classification: Despite sufficient cases being reported with the phenotype, the presence of identified variants in healthy individuals, reduced segregation of variants with the disease, inconsistencies in the reported phenotypes across cases with the same variants, and normal FAS-mediated apoptosis with variants from affected individuals suggest that this gene should not be promoted to green rating.
Cytopenia - NOT Fanconi anaemia v4.9 CASP10 Achchuthan Shanmugasundram commented on gene: CASP10: PMID:34329798 - Two patients were identified with heterozygous p.Ile406Leu variant and one was identified with p.Cys401LeufsTer15 variant. The p.Ile406Leu variant did not segregate with the disease, while the family of the patient with p.Cys401LeufsTer15 variant was not studied. The p.Ile406Leu variant, which was previously reported in several cases was found at an allele frequency of 2% in healthy individuals in certain ethnicities from the 1000 genomes database. In addition, functional assays did not show any impairment in one of these patients and five previously reported patients in comparison to healthy donors. Although p.Cys401LeufsTer15 variant was classified as likely pathogenic, it is also proposed that it is not per se causative of disease as the variant is present at higher than expected allele frequency in healthy individuals. There is also significant differences in the clinical presentations with the patient with this variant in this publication and a previously reported patient within the same variant. Another previously reported variant, p.Tyr446Cys was also present at an allele frequency of 4% in healthy individuals from 1000 genomes database, and p.Val410Ile was discarded as disease-causing by the same authors.

PMID:38704374 aimed to assess the impact of CASP10 variants on ALPS pathogenesis. Using a large cohort dataset, the authors were able to confirm that the missense variants p.Val410Ile and p.Tyr446Cys, are present in the general population at a high frequency. Furthermore, these variants do not affect the CASP10 catalytic domain and no difference was observed in CASP10 protein expression or FAS-mediated apoptosis between healthy controls and subjects bearing these variants in both homozygous and heterozygous states. Two patient had the CASP10 variant p.Cys401LeufsTer15, which lies within QACQG catalytic site in the CASP10 catalytic domain. One of the two patients was homozygous for this variant, resulting in a lack of Caspase-10 RNA and protein. However, it was reported that FAS-mediated apoptosis was comparable to healthy controls in each of the tested cell lines suspected to have a role in ALPS. In the other patient, who was heterozygous p.Cys401LeufsTer15, the authors report that although the levels of CASP10 protein expression was reduced, there was normal FAS-mediated apoptosis compared to healthy controls. From these results, it was concluded that Caspase-10 is dispensable for FAS-mediated apoptosis and an undetectable CASP10 protein expression has no impact on lymphocyte apoptosis and on individuals’ clinical and laboratory phenotype. It is also commented that post-translational or epigenetic mechanisms may play a role and yet unidentified.
Cytopenia - NOT Fanconi anaemia v4.9 FASLG Achchuthan Shanmugasundram Classified gene: FASLG as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v4.9 FASLG Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic FASLG variants with ALPS, which has cytopenia as presenting phenotype. Hence, this gene can be promoted to green rating in the next GMS update.
Cytopenia - NOT Fanconi anaemia v4.9 FASLG Achchuthan Shanmugasundram Gene: faslg has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v4.8 FASLG Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: FASLG.
Cytopenia - NOT Fanconi anaemia v4.8 FASLG Achchuthan Shanmugasundram Phenotypes for gene: FASLG were changed from ALPS to Autoimmune lymphoproliferative syndrome, type IB, OMIM:601859
Cytopenia - NOT Fanconi anaemia v4.7 FASLG Achchuthan Shanmugasundram Publications for gene: FASLG were set to
Cytopenia - NOT Fanconi anaemia v4.6 FASLG Achchuthan Shanmugasundram Mode of inheritance for gene: FASLG was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v4.5 FASLG Achchuthan Shanmugasundram reviewed gene: FASLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 8787672, 16627752, 17605793, 25451160, 26334989; Phenotypes: Autoimmune lymphoproliferative syndrome, type IB, OMIM:601859; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v4.5 FAS Achchuthan Shanmugasundram changed review comment from: FAS has a well-established gene-disease association for autosomal dominant autoimmune lymphoproliferative syndrome (ALPS) in OMIM (MIM #601859) and Gene2Phenotype (with 'definitive' rating on 'Skin disorders' panel). OMIM also reported autoimmune hemolytic anemia, thrombocytopenia and neutropenia as clinical presentations of this disorder.

This gene has also been associated with biallelic ALPS syndrome in Gene2Phenotype (with 'definitive' rating on 'Skin disorders' panel).

PMID:34171534 reviewed evidence from previously published reports, which showed that there is sufficient evidence available for the association of both monoallelic and biallelic germline variants with ALPS syndrome. There is also sufficient evidence available for the presence of autoimmune cytopenias (hemolytic anemia, thrombocytopenia and neutropenia) in both patients with both monoallelic and biallelic variants.; to: FAS has a well-established gene-disease association for autoimmune lymphoproliferative syndrome (ALPS). Both germline and somatic variants have been reported to cause ALPS.

FAS has been associated with autosomal dominant ALPS in OMIM (MIM #601859) and Gene2Phenotype (with 'definitive' rating on 'Skin disorders' panel). OMIM also reports autoimmune hemolytic anemia, thrombocytopenia and neutropenia as clinical presentations of this disorder.

This gene has also been associated with autosomal recessive ALPS syndrome in Gene2Phenotype (with 'definitive' rating on 'Skin disorders' panel).

PMID:34171534 reviewed evidence from previously published reports, which showed that there is sufficient evidence available for the association of both monoallelic and biallelic germline variants with ALPS syndrome. There is also sufficient evidence available for the presence of autoimmune cytopenias (hemolytic anemia, thrombocytopenia and neutropenia) in both patients with both monoallelic and biallelic variants.
Cytopenia - NOT Fanconi anaemia v4.5 FAS Achchuthan Shanmugasundram Classified gene: FAS as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v4.5 FAS Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants with autoimmune cytopenia. Hence, this gene can be promoted to green rating in the next GMS update.
Cytopenia - NOT Fanconi anaemia v4.5 FAS Achchuthan Shanmugasundram Gene: fas has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v4.4 FAS Achchuthan Shanmugasundram Phenotypes for gene: FAS were changed from ALPS to Autoimmune lymphoproliferative syndrome, type IA, OMIM:601859
Cytopenia - NOT Fanconi anaemia v4.3 FAS Achchuthan Shanmugasundram Publications for gene: FAS were set to
Cytopenia - NOT Fanconi anaemia v4.2 FAS Achchuthan Shanmugasundram Mode of inheritance for gene: FAS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v4.1 FAS Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: FAS.
Cytopenia - NOT Fanconi anaemia v4.1 FAS Achchuthan Shanmugasundram reviewed gene: FAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 34171534; Phenotypes: Autoimmune lymphoproliferative syndrome, type IA, OMIM:601859; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v3.34 FASLG Dmitrijs Rots gene: FASLG was added
gene: FASLG was added to Cytopenia - NOT Fanconi anaemia. Sources: Other
Mode of inheritance for gene: FASLG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FASLG were set to ALPS
Penetrance for gene: FASLG were set to Incomplete
Review for gene: FASLG was set to GREEN
Added comment: FASLG pathogenic variants (germline or somatic) causes ALPS, which has a complex phenotype including different cytopenias (mostly autoimmune).
Sources: Other
Cytopenia - NOT Fanconi anaemia v3.34 FAS Dmitrijs Rots gene: FAS was added
gene: FAS was added to Cytopenia - NOT Fanconi anaemia. Sources: Other
Mode of inheritance for gene: FAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FAS were set to ALPS
Penetrance for gene: FAS were set to Incomplete
Review for gene: FAS was set to GREEN
Added comment: FAS pathogenic variants (germline or somatic) causes ALPS, which has a complex phenotype including different cytopenias (mostly autoimmune).
Sources: Other