ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.352G>T (p.Gly118Ter)

dbSNP: rs1839957089
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Total submissions: 3
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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 RCV001057519 SCV004810418 pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2024-03-08 reviewed by expert panel curation The c.352G>T (p.Gly118Ter)(NM_001033855.3) variant in DCLRE1C is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 5/14 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). At least one patient with this variant displayed: * Diagnostic criteria for SCID/Leaky SCID/Omenn syndrome met (0.5pt) and * SCID gene panel or exome/genome sequencing conducted (0.5pt), the total is 1 point, PP4_Supporting (PMID: 37007969). This patient is compound heterozygous with c.328C>G (p.L110V), confirmed in trans (both parents tested); However, this variant has not yet been evaluated by SCID VCEP. 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, and PP4_Supporting (VCEP specifications version 1).
Labcorp Genetics (formerly Invitae), Labcorp RCV001057519 SCV001222017 pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2023-02-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly118*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 852821). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003467786 SCV004190913 pathogenic Histiocytic medullary reticulosis 2023-02-04 criteria provided, single submitter clinical testing

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