ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.1709T>G (p.Ile570Ser)

gnomAD frequency: 0.00002  dbSNP: rs769187936
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817073 SCV000957613 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 570 of the DCLRE1C protein (p.Ile570Ser). This variant is present in population databases (rs769187936, gnomAD 0.03%). 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: 659975). 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 serine 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 RCV003224477 SCV003919870 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency; Histiocytic medullary reticulosis 2021-11-22 criteria provided, single submitter clinical testing DCLRE1C NM_022487 exon 13 p.Ile455Ser (c.1364T>G): This variant has not been reported in the literature but is present in 9/33576 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs769187936). This variant amino acid serine (Ser) is present in 9 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.
Natera, Inc. RCV001830791 SCV002092734 uncertain significance Athabaskan severe combined immunodeficiency 2020-09-12 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.