ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.1733A>G (p.Tyr578Cys)

gnomAD frequency: 0.00033  dbSNP: rs778823769
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644798 SCV000766513 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 578 of the DCLRE1C protein (p.Tyr578Cys). This variant is present in population databases (rs778823769, gnomAD 0.1%). 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: 536365). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001027780 SCV001190387 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency; Histiocytic medullary reticulosis 2021-03-30 criteria provided, single submitter clinical testing DCLRE1C NM_001033855.2 exon14 p.Tyr578Cys (c.1733A>G): This variant has not been reported in the literature but is present in 0.1% (47/35438) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/10-14950753-T-C). This variant is present in ClinVar (Variation ID:536365). This variant amino acid Cysteine (Cys) is present in several species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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