Submissions for variant NM_001033855.3(DCLRE1C):c.1507_1508del (p.Ser503fs)

dbSNP: rs2131775994

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001889175	SCV002148815	pathogenic	Severe combined immunodeficiency due to DCLRE1C deficiency	2021-01-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the DCLRE1C protein. Other variant(s) that disrupt this region (p.Thr557Asnfs*21) have been determined to be pathogenic (PMID: 26476407). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with DCLRE1C-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser503Phefs*21) in the DCLRE1C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 190 amino acid(s) of the DCLRE1C protein.
PreventionGenetics, part of Exact Sciences	RCV004758200	SCV005344751	likely pathogenic	DCLRE1C-related disorder	2024-06-06	no assertion criteria provided	clinical testing	The DCLRE1C c.1507_1508delAG variant is predicted to result in a frameshift and premature protein termination (p.Ser503Phefs*21). To our knowledge, this variant has not been reported in literature or public databases. However, protein-truncating variants in DCLRE1C have been documented to be causative for severe combined immunodeficiency and are expected to be pathogenic. This variant is interpreted as likely pathogenic.