PanelApp

Activity

Filter

Cancel
Date Panel Item Activity
20 actions
Intellectual disability syndromic and non-syndromic v2.84 SMC6 chirag patel gene: SMC6 was added
gene: SMC6 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: SMC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMC6 were set to Neurodevelopmental disorder, MONDO:0700092, SMC6-related
Review for gene: SMC6 was set to AMBER
Added comment: ESHG 2026

17 affected individuals from 2 families (1 consanguineous family with 16 individuals) with biallelic variants in SMC6 (3 missense) which segregated with disease. Phenotype included microcephaly (1 family), short stature, DD/ID (1 family), dysmorphism (Seckel like), haematological anomalies (1 family), and lung disease (1 family).

SMC5/6 complex is a highly conserved multi-subunit protein complex essential for repairing DNA damage and preventing replication stress. SMC5 has been associated with a developmental disorder. SMC6 patient-derived cell lines display a shared cellular phenotype (to SMC5) typified by chromosome instability with elevated replication stress and genome instability, exacerbated when exposed to genotoxins that stabilise G-quadruplex structures. Zebrafish models showed microcephaly and reduced length.
Sources: Other
Intellectual disability syndromic and non-syndromic v2.0 SMC5 Gene migrated from ENSG00000198887 to ENSG00000198887 (gene set migration)
Intellectual disability syndromic and non-syndromic v1.750 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Neurodevelopmental disorder (MONDO#0700092), PSMC5-related to Yu-Kury neurodevelopmental syndrome, MIM# 621565
Intellectual disability syndromic and non-syndromic v1.749 PSMC5 Zornitza Stark edited their review of gene: PSMC5: Changed rating: GREEN; Changed phenotypes: Yu-Kury neurodevelopmental syndrome, MIM# 621565
Intellectual disability syndromic and non-syndromic v0.6054 PSMC5 Zornitza Stark Phenotypes for gene: PSMC5 were changed from Developmental disorders to Neurodevelopmental disorder (MONDO#0700092), PSMC5-related
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Classified gene: PSMC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6053 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6050 PSMC5 Rylee Peters reviewed gene: PSMC5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38776958, 38293138; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), PSMC5-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.5153 SMC5 Zornitza Stark Phenotypes for gene: SMC5 were changed from Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID to Atelis syndrome 2, MIM# 620185
Intellectual disability syndromic and non-syndromic v0.5152 SMC5 Zornitza Stark edited their review of gene: SMC5: Changed phenotypes: Atelis syndrome 2, MIM# 620185
Intellectual disability syndromic and non-syndromic v0.5024 SMC5 Zornitza Stark Marked gene: SMC5 as ready
Intellectual disability syndromic and non-syndromic v0.5024 SMC5 Zornitza Stark Gene: smc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5024 SMC5 Zornitza Stark Classified gene: SMC5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.5024 SMC5 Zornitza Stark Gene: smc5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.5023 SMC5 Zornitza Stark gene: SMC5 was added
gene: SMC5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SMC5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMC5 were set to 36333305
Phenotypes for gene: SMC5 were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, SLF2-related; Atelis syndrome; microcephaly; short stature; ID
Review for gene: SMC5 was set to GREEN
Added comment: Four individuals from three families with a chromosome breakage disorder and bi-allelic variants in this gene. However, three of the individuals had the same homozygous missense variant. Evidence for functional impact of the variant was limited. However, zebrafish model recapitulated the phenotype and was not rescued by the introduction of this variant, arguing for functional effect. Borderline Amber/Green.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Marked gene: PSMC5 as ready
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Classified gene: PSMC5 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.3158 PSMC5 Zornitza Stark Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.3157 PSMC5 Zornitza Stark gene: PSMC5 was added
gene: PSMC5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC5 were set to 33057194
Phenotypes for gene: PSMC5 were set to Developmental disorders
Review for gene: PSMC5 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 9 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating).
Sources: Literature