ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.597C>A (p.Tyr199Ter)

dbSNP: rs121908157
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000256066 SCV000321543 pathogenic not provided 2018-07-23 criteria provided, single submitter clinical testing The Y199X nonsense variant in the DCLRE1C gene has been reported previously, as Y192X, in association with Severe Combined Immune Deficiency (SCID) with Radiation Sensitivity (Li et al., 2002). It is a common pathogenic variant in Native Americans of the Athabascan language group, which includes Navajo, Apache and other Native American groups in western North America. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional studies have shown that Y199X severely impairs the function of the DCLRE1C protein (Felgentreff et al., 2015).
Invitae RCV000703249 SCV000832142 pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2023-07-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 4673). This premature translational stop signal has been observed in individuals with severe combined immunodeficiency (PMID: 12055248, 25762520). It is commonly reported in individuals of Navajo and Apache Native American ancestry (PMID: 12055248). This variant is present in population databases (rs121908157, gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr199*) in the DCLRE1C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DCLRE1C are known to be pathogenic (PMID: 21664875, 26123418).
Baylor Genetics RCV003466818 SCV004190883 pathogenic Histiocytic medullary reticulosis 2023-10-18 criteria provided, single submitter clinical testing
OMIM RCV000004937 SCV000025113 pathogenic Athabaskan severe combined immunodeficiency 2002-06-15 no assertion criteria provided literature only
Natera, Inc. RCV000004937 SCV002081503 pathogenic Athabaskan severe combined immunodeficiency 2020-09-03 no assertion criteria provided clinical testing

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