Submissions for variant NM_001033855.3(DCLRE1C):c.1265C>A (p.Ser422Ter)

dbSNP: rs1354336544

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001232221	SCV001404769	pathogenic	Severe combined immunodeficiency due to DCLRE1C deficiency	2023-02-04	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DCLRE1C protein in which other variant(s) (p.Cys436*) have been determined to be pathogenic (PMID: 20674517, 22527898, 25917813, 29167666). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 958957). This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser422*) in the DCLRE1C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 271 amino acid(s) of the DCLRE1C protein.
Baylor Genetics	RCV003469418	SCV004190903	likely pathogenic	Histiocytic medullary reticulosis	2024-02-24	criteria provided, single submitter	clinical testing