ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.140T>A (p.Leu47Ter)

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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 RCV003032800 SCV004242285 likely pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2024-01-23 reviewed by expert panel curation The c.140T>A (p.Leu47Ter)(NM_001033855.3) variant in DCLRE1C is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 2/14 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 v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions or in functional studies. In summary, this variant meets the criteria to be classified as Likely 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: PM2_Supporting and PVS1 (VCEP specifications version 1).
Invitae RCV003032800 SCV003330962 pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2022-03-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. This sequence change creates a premature translational stop signal (p.Leu47*) 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).

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