ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.247A>G (p.Ile83Val)

dbSNP: rs746658739
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV002020966 SCV004810404 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2024-02-15 reviewed by expert panel curation The c.247A>G (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause the substitution of Isoleucine by Valine at amino acid 83 (p.Ile83Val). The filtering allele frequency (the upper threshold of the 95% CI of 3/84132 alleles) of the c.247A>G variant in DCLRE1C is 0.000009470 for South Asian chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). No homozygotes have been observed in gnomAD. Another missense variant NM_001033855.3(DCLRE1C):c.247A>C (p.Ile83Leu) in the same codon has been reported; However, this variant was classified as VUS by the ClinGen SCID VCEP (PM5 not met). 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: PM2_Supporting (VCEP specifications version 1).
Labcorp Genetics (formerly Invitae), Labcorp RCV002020966 SCV002298243 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 83 of the DCLRE1C protein (p.Ile83Val). This variant is present in population databases (rs746658739, gnomAD 0.003%). 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: 1515264). 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 valine 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.

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.