ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.181T>C (p.Cys61Arg)

dbSNP: rs1589136760
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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 RCV000802746 SCV004810436 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2024-02-15 reviewed by expert panel curation The c.181T>C (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Cysteine by Arginine at amino acid 61 (p.Cys61Arg). This variant is absent from gnomAD v4 (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 a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: PM2_Supporting (VCEP specifications version 1.0).
Labcorp Genetics (formerly Invitae), Labcorp RCV000802746 SCV000942589 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2022-03-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 61 of the DCLRE1C protein (p.Cys61Arg). 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: 648095). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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