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Primary immunodeficiency or monogenic inflammatory bowel disease v9.102 NFATC2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are only two unrelated cases published with biallelic NFATC2 variants and with a relevant phenotype. They displayed phenotypic variability with both displaying lymphoproliferative disorder, but only one with skeletal phenotype. Hence, this gene should be rated amber with the current evidence.; to: Comment on list classification: There are only two unrelated cases published with biallelic NFATC2 variants and with a relevant phenotype. They displayed phenotypic variability with both displaying lymphoproliferative disorder, but only one with skeletal phenotype. Hence, this gene should be rated amber with the current evidence.

The 'watchlist' tag has been added as there is an additional patient reported in a conference abstract with relevant phenotype. Hence, this gene should be reviewed and updated when additional published evidence become available.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.102 NFATC2 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: NFATC2.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.95 NFATC2 Achchuthan Shanmugasundram Classified gene: NFATC2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v9.95 NFATC2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are only two unrelated cases published with biallelic NFATC2 variants and with a relevant phenotype. They displayed phenotypic variability with both displaying lymphoproliferative disorder, but only one with skeletal phenotype. Hence, this gene should be rated amber with the current evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.95 NFATC2 Achchuthan Shanmugasundram Gene: nfatc2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v9.94 NFATC2 Achchuthan Shanmugasundram Publications for gene: NFATC2 were set to 35789258
Primary immunodeficiency or monogenic inflammatory bowel disease v9.93 NFATC2 Achchuthan Shanmugasundram Phenotypes for gene: NFATC2 were changed from progressive joint contractures; osteochondromas; B cell malignancy; diarrhea; chronic lung disease; hypogammaglobulinemia to ?Joint contracture, osteochondromas, and B-cell lymphoma, OMIM:620232; joint contractures, osteochondromas, and B-cell lymphoma, MONDO:0859369; lymphoproliferative syndrome, MONDO:0016537
Primary immunodeficiency or monogenic inflammatory bowel disease v9.92 NFATC2 Achchuthan Shanmugasundram reviewed gene: NFATC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35789258, 38427060; Phenotypes: ?Joint contracture, osteochondromas, and B-cell lymphoma, OMIM:620232, joint contractures, osteochondromas, and B-cell lymphoma, MONDO:0859369, lymphoproliferative syndrome, MONDO:0016537; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v9.9 NFATC2 Boaz Palterer gene: NFATC2 was added
gene: NFATC2 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258
Phenotypes for gene: NFATC2 were set to progressive joint contractures; osteochondromas; B cell malignancy; diarrhea; chronic lung disease; hypogammaglobulinemia
Penetrance for gene: NFATC2 were set to unknown
Review for gene: NFATC2 was set to RED
Added comment: NFATC2 (also known as NFAT1) encodes the nuclear factor of activated T cells 2, a critical calcium/calcineurin-dependent transcription factor essential for T cell activation, immune homeostasis, and cell fate regulation.

Sharma et al. identified 1 patient from 1 family carrying a homozygous pathogenic NFATC2 frameshift variant (p.Tyr675Thrfs*18) presenting with progressive joint contractures, osteochondromas, and B cell malignancy.

Bustamante-Ogando et al. identified 1 patient from 1 family carrying compound heterozygous NFATC2 missense variants (p.Gly408Arg/p.Arg646Gln) presenting with severe early-onset immunodeficiency, recurrent sinopulmonary infections, bloody diarrhea, chronic lung disease, and pan-hypogammaglobulinemia.
( https://doi.org/10.70962/LASID2025abstract.69 )
Sources: Literature