Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001313913.2:c.1189T>G

CA414447216

Gene: F9 (HGNC:2158)

Condition: hemophilia B (MONDO:0010604)

Inheritance Mode: X-linked inheritance

UUID: 791488da-e5d8-4596-95b1-53079e87e817

Approved on: 2024-05-09

Published on: 2024-07-11

HGVS expressions

NM_001313913.2:c.1189T>G

NC_000023.11:g.139561988T>G

CM000685.2:g.139561988T>G

NC_000023.10:g.138644147T>G

CM000685.1:g.138644147T>G

NC_000023.9:g.138471813T>G

NG_007994.1:g.36253T>G

ENST00000218099.7:c.1303T>G

ENST00000643157.1:n.1723+247T>G

ENST00000218099.6:c.1303T>G

ENST00000394090.2:c.1189T>G

NM_000133.3:c.1303T>G

NM_001313913.1:c.1189T>G

NM_000133.4:c.1303T>G

Likely Pathogenic

PM2_Supporting PS4_Moderate PP3 PM5

PM1

Evidence Links 0

Expert Panel

Coagulation Factor Deficiency VCEP

Criteria Specification Information

Criteria Specification: ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Coagulation Factor Deficiency VCEP

The F9 c.1303T>G; p.Cys435Gly variant is completely absent from gnomAD v2.1.1 and v3.1.1. This missense variant has a REVEL score of 0.964 and meets PP3 criteria (threshold >0.6). One proband is reported in the literature with moderate hemophilia B and this variant and a second proband was reported with severe hemophilia B, meeting F9 phenotype criteria for PS4_Moderate. Cys35Tyr is another pathogenic variant at the same residue (PM5). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F9: PS4_Moderate, PM5, PP3, PM2_Supporting.

PM2_Supporting

Variant is absent from gnomAD v2.1.1 and 3.1.

PS4_Moderate

2 probands with hemophilia B (one severe and one moderate) in the literature.

PP3

REVEL score is 0.964, which is above the 0.6 cutoff.

PM5

The F9 c. Cys435Tyr variant reaches a pathogenic classification by the CFD VCEP rule specifications.

PM1

Variant is not within exons 3, 4 or 5.

Curation History

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