ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.597C>A (p.Tyr199Ter) (rs121908157)

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Total submissions: 3
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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 2019-12-23 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (ExAC no frequency). This variant has been reported as a founder mutation in Navajo and Apache Native Americans (PMID: 12055248) and has been observed as homozygous in several individuals affected with severe combined immunodeficiency (PMID: 25762520). ClinVar contains an entry for this variant (Variation ID: 4673). Loss-of-function variants in DCLRE1C are known to be pathogenic (PMID: 21664875, 26123418). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004937 SCV000025113 pathogenic Severe combined immunodeficiency, athabascan-type 2002-06-15 no assertion criteria provided literature only

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