Submissions for variant NM_006659.4(TUBGCP2):c.1145C>T (p.Ala382Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV003151681	SCV003839193	uncertain significance	not specified	2022-12-02	no assertion criteria provided	clinical testing	DNA sequence analysis of the TUBGCP2 gene demonstrated a sequence change, c.1229C>T, in exon 9 that results in an amino acid change, p.Ala410Val. This sequence change does not appear to have been previously described in individuals with TUBGCP2-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.57% in the Finnish subpopulation (dbSNP rs199910091). The p.Ala410Val change affects a highly conserved amino acid residue located in a domain of the TUBGCP2 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ala410Val substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Ala410Val change remains unknown at this time. Bi-allelic pathogenic variants in TUBGCP2 have been reported in individuals with microcephaly, developmental delay, and cortical brain malformations (PMID: 31630790, 33458610)
PreventionGenetics, part of Exact Sciences	RCV003936714	SCV004747892	likely benign	TUBGCP2-related disorder	2021-03-12	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).