ClinVar Miner

Submissions for variant NM_000892.5(KLKB1):c.1204_1205del (p.Trp402fs)

dbSNP: rs768319200
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz RCV002467395 SCV002761960 pathogenic Inherited prekallikrein deficiency 2022-12-06 criteria provided, single submitter clinical testing We have detected this variant, NM_000892.4(KLKB1):c.1204_1205delTG p.(Trp402Alafs*35), in two siblings via Sanger sequencing in heterozygosity (PMID: 32202057; slightly misnamed as c.1203_1204delGT, since the 3'-rule was not followed). Their aPTTs were within the usual reference ranges but they showed slightly decreased prekallikrein (PK) levels (case1: 66% PK activity, 43% PK antigen; case2: 59% PK activity, 34% PK antigen). Their father was known to be completely PK deficient (5% PK activity, 2% PK antigen) and was published by Asmis et al (PMID: 12091043). This small deletion has a global MAF of ~0.01% (dbSNP) and likely results in a frameshift at protein level with a premature stop codon. In addition, it includes a base position that has already been described as a cause of PK deficiency in the literature in a compound heterozygous case (PMID: 14652634). Therefore, we classified this variant as pathogenic in accordance with ACMG guidelines.
PreventionGenetics, part of Exact Sciences RCV003395482 SCV004120535 likely pathogenic KLKB1-related disorder 2023-01-27 criteria provided, single submitter clinical testing The KLKB1 c.1204_1205delTG variant is predicted to result in a frameshift and premature protein termination (p.Trp402Alafs*35). This variant was reported in an individual with Prekallikrein (PK) deficiency; however, zygosity of this variant was not clearly established in this patient (Case #4 in Barco et al. 2020. PubMed ID: 32202057). This variant is reported in 0.026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-187173228-AGT-A). Frameshift variants in KLKB1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV002467395 SCV005918669 likely pathogenic Inherited prekallikrein deficiency 2022-08-29 criteria provided, single submitter research

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.