Submissions for variant NM_001033855.3(DCLRE1C):c.1299_1306dup (p.Cys436Ter)

dbSNP: rs2131778656

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001383395	SCV001582528	pathogenic	Severe combined immunodeficiency due to DCLRE1C deficiency	2022-10-04	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1071047). 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.Gly464Alafs*18) have been observed in individuals with DCLRE1C-related conditions (PMID: 18034425). This suggests that this may be a clinically significant region of the protein. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on DCLRE1C function (PMID: 25917813). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This variant is also known as 1307 AGGATGCT 1308 (p.436C > X) and 1306ins8 p.C330X. This premature translational stop signal has been observed in individuals with severe combined immunodeficiency (SCID) and "leaky" SCID (PMID: 20674517, 22527898, 29167666). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys436*) in the DCLRE1C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 257 amino acid(s) of the DCLRE1C protein.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001383395	SCV004806862	pathogenic	Severe combined immunodeficiency due to DCLRE1C deficiency	2024-03-26	criteria provided, single submitter	clinical testing