Submissions for variant NM_001375524.1(TRRAP):c.5713A>G (p.Lys1905Glu)

dbSNP: rs1791437854

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn	RCV001250480	SCV001371844	likely pathogenic	Developmental delay with or without dysmorphic facies and autism; TRAPP-associated developmental delay		criteria provided, single submitter	clinical testing	By means of trio-exome sequencing and analysis of the genes with the ten highest PEDIA values (PMID: 31164752), a missense variant in exon 39 of the TRRAP gene, which probably causes the disease, was detected in this patient. The name of the variant is: NM_001244580.1:c.5692A>G; p.(Lys1898Glu). For the parents, this variant could not be proven, which is why it is highly probable that the patient developed it anew (de novo). This variant has not yet been recorded in population-based and phanotype-based databases. The mutation prediction programs MutationTaster, SIFT and PolyPhen-2 classify the above-mentioned variant as pathogenic; the CADD score is 29.5. According to the gnomAD database, missense variants are extremely rare in the TRRAP gene, and in phanotype-related databases and publications, missense variants in particular are currently classified as pathogenic in the TRRAP gene. The ACMG classification of the variant is: probably pathogenic (class 4: PS2, PM2, PP2, PP3).
Laboratory of Medical Genetics, University of Torino	RCV002464419	SCV002760150	uncertain significance	Developmental delay with or without dysmorphic facies and autism	2022-11-29	criteria provided, single submitter	research