ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.522C>G (p.Tyr174Ter)

dbSNP: rs1340132582
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV000814078 SCV004810425 pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2024-03-08 reviewed by expert panel curation The c.522C>G (p.Tyr174Ter)(NM_001033855.3) variant in DCLRE1C is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 7/14 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1 is met). This variant is absent from gnomAD v4 (PM2_Supporting). One patient reported in the literature is homozygous for this variant, 0.5 pts, PM3_Supporting. She is T-B-NK+ (0.5 pts) with diagnosis carried out through SCID gene panel or exome/genome sequencing conducted (0.5 pts), total 1 pt, PP4_Supporting (PMID: 37480474). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PVS1, PM2_Supporting, PM3_Supporting, and PP4_Supporting (VCEP specifications version 1).
Labcorp Genetics (formerly Invitae), Labcorp RCV000814078 SCV000954475 pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2018-10-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr174*) in the DCLRE1C gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DCLRE1C are known to be pathogenic (PMID: 21664875, 26123418). This variant has not been reported in the literature in individuals with DCLRE1C-related disease. This variant is not present in population databases (ExAC no frequency).

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