ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.1669dup (p.Thr557fs)

dbSNP: rs886037924
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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 RCV000240842 SCV004102779 likely pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2023-11-14 reviewed by expert panel curation The NM_001033855.3(DCLRE1C):c.1669dup (p.Thr557AsnfsTer21) variant in DCLRE1C is a frameshift variant that may cause loss of function of the protein; however, it is predicted that the transcript likely escapes nonsense-mediated decay (PMID: 26476407 supports this notion). Additionally, no downstream pathogenic variants have been curated to date (curated following SCID VCEP specifications). Thus, currently, this variant is limited to PVS1 at moderate strength. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). There are 2 patients who are siblings (Family A, P4, and P5) (PMID: 26476407, PP1_supporting). At least one patient with this variant displayed Vector-based complementation corrected increased cellular radiosensitivity and/or decreased V(D)J recombination (P5, 2 pts, PMID:26476407, PP4_Moderate). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive SCID based on the ACMG/AMP criteria applied: PVS1_Moderate, PM2_Supporting, PP1_Supporting, and PP4_Moderate, as specified by the ClinGen SCID VCEP (VCEP specifications version 1).
OMIM RCV000240842 SCV000299329 pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency 2016-09-14 no assertion criteria provided literature only

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