ClinVar Miner

Submissions for variant NM_000569.8(FCGR3A):c.197T>A (p.Leu66His)

gnomAD frequency: 0.04855  dbSNP: rs10127939
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000454581 SCV000539166 uncertain significance 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: High frequency in the general population (5 homozygotes in ExAC), but homozygous change at this position has been reported in 3 individuals with NK cell deficiency. 2 probands had recurrent upper respiratory infections. In vitro study shows possible functional impact (PMID 23006327).
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000015953 SCV000898708 uncertain significance Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity 2021-03-30 criteria provided, single submitter clinical testing FCGR3A NM_1127593.1 exon 4 p.Leu66His (c.197T>A): This variant has been reported in the literature as homozygous in 3 individuals with recurrent infection, suggestive of NK cell defects (de Vries 1996 PMID:8874200, Jawahar 1996 PMID:8608639, Grier 2012 PMID:23006327, called c.230T>A p.Leu66His). This variant is present in 7.5% (9575/126258) of European alleles including 17 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs10127939). This variant is present in ClinVar (Variation ID:14828). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, although this variant is present at a high frequency in the general population, the presence of conflicting data on this variant suggests insufficient information for disease classification. Therefore, the clinical significance of this variant is uncertain.
Breakthrough Genomics, Breakthrough Genomics RCV004691094 SCV005187020 uncertain significance not provided criteria provided, single submitter not provided
OMIM RCV000015953 SCV000036220 pathogenic Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity 2012-10-01 no assertion criteria provided literature only

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