ClinVar Miner

Submissions for variant NM_012452.2(TNFRSF13B):c.563A>T (p.Lys188Met) (rs74811083)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224878 SCV000280801 likely benign not provided 2015-08-17 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000355524 SCV000400915 likely benign Common Variable Immune Deficiency, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780778 SCV000918319 benign not specified 2018-08-22 criteria provided, single submitter clinical testing Variant summary: TNFRSF13B c.563A>T (p.Lys188Met) results in a non-conservative amino acid change located in the intracellular domain (Fried 2011) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0046 in 276498 control chromosomes in the gnomAD database, including 27 homozygotes. The observed variant frequency is approximately 1600 fold above the estimated maximal expected allele frequency for a pathogenic variant in TNFRSF13B causing Common Variable Immunodeficiency (CVID) phenotype (2.9e-06), strongly suggesting that the variant is benign. Though c.563A>T has been reported in the literature in individual(s) affected with sporadic CVID (Grimbacher 2006), this report does not provide unequivocal conclusions about association of the variant with CVID. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant for protein expression, ligand binding and signaling function (Fried 2011). 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.
Invitae RCV000539431 SCV000649858 benign Common variable immunodeficiency 2 2017-11-01 criteria provided, single submitter clinical testing

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