ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.1350_1356del (p.Asp451fs)

dbSNP: rs786200884
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644797 SCV000766512 pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2020-10-09 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the DCLRE1C gene (p.Asp451Lysfs*11). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 242 amino acids of the DCLRE1C protein. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant results in reduced recombination activity, reduced DNA repair activity (following ionizing radiation), and elevated interchromosomal V(D)J rearrangements when compared to wildtype (PMID: 25917813, 21147755). This variant does maintain some residual hairpin activity (PMID: 21147755). However, mouse models of this variant exhibit reduced numbers of B and T lymphocytes, thereby recapitulating the human phenotype (PMID: 19953608). This variant has been reported to segregate in a family with combined immunodeficiency characterized by severe T and B lymphocytopenia and upper/lower respiratory infections (PMID: 12569164). This variant is also known as D451fsX10 and Artemis P70 in the literature. ClinVar contains an entry for this variant (Variation ID: 4675). This variant is not present in population databases (ExAC no frequency).
Baylor Genetics RCV003466819 SCV004190916 pathogenic Histiocytic medullary reticulosis 2022-11-23 criteria provided, single submitter clinical testing
OMIM RCV000004939 SCV000025115 pathogenic Severe combined immunodeficiency, partial 2003-02-01 no assertion criteria provided literature only
Natera, Inc. RCV001826416 SCV002084115 pathogenic Athabaskan severe combined immunodeficiency 2021-01-07 no assertion criteria provided clinical testing

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