ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.1990C>T (p.Arg664Ter)

gnomAD frequency: 0.00012  dbSNP: rs200693133
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001241274 SCV001414283 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2021-02-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the DCLRE1C gene (p.Arg664*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acids of the DCLRE1C protein. This variant is present in population databases (rs200693133, ExAC 0.006%). This variant has not been reported in the literature in individuals with DCLRE1C-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.
Fulgent Genetics, Fulgent Genetics RCV002499401 SCV002792384 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency; Histiocytic medullary reticulosis 2022-02-07 criteria provided, single submitter clinical testing
Lifecell International Pvt. Ltd RCV001241274 SCV003930271 likely pathogenic Severe combined immunodeficiency due to DCLRE1C deficiency criteria provided, single submitter clinical testing A Heterozygous Nonsense variant c.1645C>T in Exon 13 of the DCLRE1C gene that results in the amino acid substitution p.Arg549* was identified. The observed variant has a maximum allele frequency of 0.00004/0.00010% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Uncertain Significance [Variant ID: 966558]. For these reasons, this variant has been classified as Likely Pathogenic.
Natera, Inc. RCV001828972 SCV002094715 uncertain significance Athabaskan severe combined immunodeficiency 2020-12-28 no assertion criteria provided clinical testing

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