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| Severe microcephaly v8.25 | TM2D3 |
Achchuthan Shanmugasundram changed review comment from: PMID:40449487 (2025) reported four unrelated individuals with overlapping clinical presentations, including microcephaly, severe global developmental delay with absent speech, autistic features, heart malformation, and dysmorphic facial features. Microcephaly was severe in three of four patients (beyond -3 SD), while it is -2.5 SD in the fourth patient. They were all identified with homozygous or compound heterozygous variants in TM2D3 gene via exome sequencing. There is also functional evidence available from SNB75 TM2D3-knockout cells as well as skin fibroblasts from affected individuals harbouring the recurrent c.503G>A (p.Gly168Asp) allele. This gene has been associated with relevant phenotype in OMIM (MIM #621379, last accessed 02 January 2026) and Gene2Phenotype (with 'moderate' rating on DD panel), but not yet in ClinGen. Sources: Literature; to: PMID:40449487 (2025) reported four unrelated individuals with overlapping clinical presentations, including microcephaly, severe global developmental delay with absent speech, autistic features, heart malformation, and dysmorphic facial features. Microcephaly was severe in three of four patients (OFC beyond -3 SD), while OFC is -2.5 SD in the fourth patient. They were all identified with homozygous or compound heterozygous variants in TM2D3 gene via exome sequencing. There is also functional evidence available from SNB75 TM2D3-knockout cells as well as skin fibroblasts from affected individuals harbouring the recurrent c.503G>A (p.Gly168Asp) allele. This gene has been associated with relevant phenotype in OMIM (MIM #621379, last accessed 02 January 2026) and Gene2Phenotype (with 'moderate' rating on DD panel), but not yet in ClinGen. Sources: Literature |
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| Severe microcephaly v8.25 | TM2D3 | Achchuthan Shanmugasundram Classified gene: TM2D3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.25 | TM2D3 | Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated patients reported with severe microcephaly (OFC beyond -3 SD). Hence, this gene can be promoted to green rating in the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.25 | TM2D3 | Achchuthan Shanmugasundram Gene: tm2d3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.24 | TM2D3 | Achchuthan Shanmugasundram Tag Q1_26_promote_green tag was added to gene: TM2D3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v8.24 | TM2D3 |
Achchuthan Shanmugasundram gene: TM2D3 was added gene: TM2D3 was added to Severe microcephaly. Sources: Literature Mode of inheritance for gene: TM2D3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TM2D3 were set to 40449487 Phenotypes for gene: TM2D3 were set to Neurocardiorenal malformation syndrome, OMIM:621379 Review for gene: TM2D3 was set to GREEN Added comment: PMID:40449487 (2025) reported four unrelated individuals with overlapping clinical presentations, including microcephaly, severe global developmental delay with absent speech, autistic features, heart malformation, and dysmorphic facial features. Microcephaly was severe in three of four patients (beyond -3 SD), while it is -2.5 SD in the fourth patient. They were all identified with homozygous or compound heterozygous variants in TM2D3 gene via exome sequencing. There is also functional evidence available from SNB75 TM2D3-knockout cells as well as skin fibroblasts from affected individuals harbouring the recurrent c.503G>A (p.Gly168Asp) allele. This gene has been associated with relevant phenotype in OMIM (MIM #621379, last accessed 02 January 2026) and Gene2Phenotype (with 'moderate' rating on DD panel), but not yet in ClinGen. Sources: Literature |
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