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]

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Variant: NM_001313913.2:c.1211G>C

CA414447351

Gene: F9

Condition: hemophilia B

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 045fd8d6-4244-4e24-84e2-155124e0762b

Approved on: 2024-05-09

Published on: 2024-07-11

HGVS expressions

NM_001313913.2:c.1211G>C

NC_000023.11:g.139562010G>C

CM000685.2:g.139562010G>C

NC_000023.10:g.138644169G>C

CM000685.1:g.138644169G>C

NC_000023.9:g.138471835G>C

NG_007994.1:g.36275G>C

ENST00000218099.7:c.1325G>C

ENST00000643157.1:n.1723+269G>C

ENST00000218099.6:c.1325G>C

ENST00000394090.2:c.1211G>C

NM_000133.3:c.1325G>C

NM_001313913.1:c.1211G>C

NM_000133.4:c.1325G>C

Likely Pathogenic

PS4 PP3 PM5 PM2_Supporting

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 c.1325G>C (NM_000133.4) variant in F9 is a missense variant predicted to cause substitution of Glycine by Alanine at amino acid 442 (p.Gly442Ala). This variant has been reported in at least 4 probands meeting the hemophilia B phenotype criteria specified by the Coagulation Factor Deficiency VCEP (PS4_Moderate; PMID: 7937052, poster https://www.postersessiononline.eu/173580348_eu/congresos/WFH2018/aula/-M-P_49_WFH2018.pdf, internal laboratory data). This variant is absent from gnomAD v2.1.1 and v3.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.884, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3). Another missense variant c.1234G>A, p.Gly442Arg in the same codon has been classified as pathogenic for hemophilia B by the ClinGen Coagulation Factor Deficiency VCEP (PM5). In summary, this variant meets the criteria to be classified as Likely Pathogenic for X-linked recessive hemophilia B based on the ACMG/AMP criteria applied, as specified by the ClinGen Coagulation Factor Deficiency VCEP: PS4, PM5, PP3, PM2_Supporting. (ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0., Released 10/5/2023)

PS4

This variant has been reported in at least 4 probands meeting the hemophilia B phenotype criteria specified by the Coagulation Factor Deficiency VCEP (PS4; PMID: 7937052, poster https://www.postersessiononline.eu/173580348_eu/congresos/WFH2018/aula/-M-P_49_WFH2018.pdf, and internal laboratory data).

PP3

The computational predictor REVEL gives a score of 0.884, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3). SpliceAI predicts no impact on splicing with a delta score of 0.

PM5

Another missense variant c.1234G>A, p.Gly442Arg in the same codon has been classified as pathogenic for hemophilia B by the ClinGen Coagulation Factor Deficiency VCEP (PM5).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 and v3.1.1 (PM2_Supporting).

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