Submissions for variant NM_000531.6(OTC):c.387-2A>T

dbSNP: rs66556380

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000011745	SCV003444646	pathogenic	Ornithine carbamoyltransferase deficiency	2022-10-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the OTC protein in which other variant(s) (p.Ser132Tyr) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in exon 5 (PMID: 2035531). Studies have shown that disruption of this splice site alters OTC gene expression (PMID: 2035531). ClinVar contains an entry for this variant (Variation ID: 10998). Disruption of this splice site has been observed in individuals with ornithine transcarbamylase deficiency (PMID: 2035531, 10946359). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 4 of the OTC gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 3 amino acid residue(s), but is expected to preserve the integrity of the reading-frame.
OMIM	RCV000011745	SCV000031977	pathogenic	Ornithine carbamoyltransferase deficiency	1991-06-01	no assertion criteria provided	literature only
GenMed Metabolism Lab	RCV000083419	SCV000115505	pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Pathogenic.