ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.457G>A (p.Gly153Arg) (rs41297018)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000455778 SCV000052308 benign not specified 2018-03-09 criteria provided, single submitter clinical testing Variant summary: DCLRE1C c.457G>A (p.Gly153Arg) results in a non-conservative amino acid change located in the Metallo-beta-lactamase domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.011 in 120654 control chromosomes in the ExAC database, including 12 homozygotes. The observed variant frequency is approximately 2.72 fold of the estimated maximal expected allele frequency for a pathogenic variant in DCLRE1C causing Severe Combined Immunodeficiency Syndrome phenotype (0.0041), strongly suggesting that the variant is benign. c.457G>A has been reported in the literature in individuals affected with Severe Combined Immunodeficiency Syndrome. These report(s) do not provide unequivocal conclusions about association of the variant with Severe Combined Immunodeficiency Syndrome. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224125 SCV000280758 likely benign not provided 2015-09-02 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455778 SCV000538776 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant associated with SCID, but high frequency and a functional study suggests no impact on activity.
Invitae RCV000560374 SCV000645228 benign Severe combined immunodeficiency due to DCLRE1C deficiency 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000455778 SCV000720401 benign not specified 2017-01-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Mendelics RCV000560374 SCV001138004 benign Severe combined immunodeficiency due to DCLRE1C deficiency 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000455778 SCV001156850 benign not specified 2019-06-10 criteria provided, single submitter clinical testing

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