ClinVar Miner

Submissions for variant NM_000132.4(F8):c.5217C>T (p.Asn1739=)

dbSNP: rs1603433715
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen RCV004808871 SCV005431483 likely pathogenic Hereditary factor VIII deficiency disease 2024-10-11 reviewed by expert panel curation The NM_000132.3(F8):c.5217C>T (p.Asn1739=) synonymous variant is completely absent from population databases (gnomAD v2.1.1/gnomAD v3.1.1). SpliceAI predicts a score of 0.31 for the loss of the canonical donor of intron 14; however the threshold (>0.5) for SpliceAI is not met and does not meet criteria for PP3. At least 4 probands with mild hemophilia A from the literature and internal laboratory data meet F8-phenotype criteria. This variant was found to co-segregate with disease in affected family members, with two meioses observed in a family (Internal Laboratory Data), meeting criteria for PP1. In summary, this variant meets the criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8: PS4, PP1, PM2_Supporting. (ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F8 Version 1.0.0., Released 10/5/2023).
NIHR Bioresource Rare Diseases, University of Cambridge RCV000852146 SCV000899786 likely pathogenic Hereditary factor IX deficiency disease 2019-02-01 criteria provided, single submitter research

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