ClinVar Miner

Submissions for variant NM_001102416.3(KNG1):c.306+2T>A

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz RCV003325634 SCV004031439 pathogenic High molecular weight kininogen deficiency 2023-09-04 criteria provided, single submitter clinical testing This canonical splice site variant, NM_001102416.3(KNG1):c.306+2T>A, was detected in a homozygous individual deficient in high-molecular-weight kininogen (<2% HK activity, <1% HK antigen, prolonged aPTT) (PMID: 36700498) using Sanger Sequncing. Gros deletions and insertions in the corresponding area were excluded using ddPCR. The two children of the index case are heterozygous carriers of the variant and show slightly decreased HK antigen levels (37-44%). The variant has otherwise not been described in the literature and is not included in the dbSNP, which is why a very low MAF can be assumed. Predictions tools predict pathogenicity. Due to the location of the variant, a combined deficiency of HK and low-molecular-weight kininogen is likely. The base exchange affects the canonical, highly conserved donor splice site of IVS 2. Therefore, we classified this variant as pathogenic.

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