ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.589A>G (p.Ser197Gly)

gnomAD frequency: 0.00002  dbSNP: rs1252776122
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
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 RCV000809196 SCV005375423 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2024-06-13 reviewed by expert panel curation The c.589A>G (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Serine by Glycine at amino acid 197 (p.Ser197Gly). The filtering allele frequency (the upper threshold of the 95% CI of 6/59982) of the c.589A>G variant in DCLRE1C is 0.00004285 for Admixed American chromosomes by gnomAD v4, which is lower than the SCID-VCEP threshold for BS1 (>0.00078) and BA1 (>0.00346) but higher than the threshold (<0.00003266) for PM2_Supporting (BS1 not met, BA1 not met, PM2_Supporting not met). No homozygotes have been observed in gnomAD. To our knowledge, this variant has not been reported in the literature in individuals affected with SCID/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 (specification version 1.0): No criteria were applied.
Labcorp Genetics (formerly Invitae), Labcorp RCV000809196 SCV000949339 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2022-05-31 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 197 of the DCLRE1C protein (p.Ser197Gly). This variant is present in population databases (no rsID available, 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: 653423). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002537308 SCV003648361 uncertain significance Inborn genetic diseases 2022-09-27 criteria provided, single submitter clinical testing The c.589A>G (p.S197G) alteration is located in exon 8 (coding exon 8) of the DCLRE1C gene. This alteration results from a A to G substitution at nucleotide position 589, causing the serine (S) at amino acid position 197 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001825613 SCV002079302 uncertain significance Athabaskan severe combined immunodeficiency 2020-10-19 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.