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.838C>T

CA414444915

Gene: F9 (HGNC:2158)

Condition: hemophilia B (MONDO:0010604)

Inheritance Mode: X-linked inheritance

UUID: 28772313-2391-433a-85eb-86a59f7a4dd8

Approved on: 2024-10-11

Published on: 2024-11-01

HGVS expressions

NM_001313913.2:c.838C>T

NC_000023.11:g.139561637C>T

CM000685.2:g.139561637C>T

NC_000023.10:g.138643796C>T

CM000685.1:g.138643796C>T

NC_000023.9:g.138471462C>T

NG_007994.1:g.35902C>T

ENST00000218099.7:c.952C>T

ENST00000643157.1:n.1619C>T

ENST00000218099.6:c.952C>T

ENST00000394090.2:c.838C>T

NM_000133.3:c.952C>T

NM_001313913.1:c.838C>T

NM_000133.4:c.952C>T

Pathogenic

PS2 PS4 PP3 PM2_Supporting

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 c.952C>T; p.Leu318Phe variant is completely absent from gnomAD v2.1.1 and v3.1.1. This missense variant has a REVEL score of 0.943 and meets PP3 criteria (threshold >0.6). At least 4 patients are reported in the literature with moderate-severe hemophilia B and this variant, meeting F9 phenotype criteria for PS4. There is at least 1 proband with isolated reduction in FIX activity levels meeting phenotypic criteria for F9, with confirmed de novo (maternity confirmed in an affected male) occurrence (PMID: 30648777). In summary, this variant meets criteria to be classified as pathogenic. The ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel, for F9: PS4, PS2, PP3, PM2_Supporting.

PS2

Lu, 2019 PMID: 30648777 is de novo (maternity confirmed), meets 2 points SVI PS2/PM6 chart = PS2

PS4

At least four probands have been identified with this variant and moderate/severe hemophilia B.

PP3

REVEL score is 0.943 which is above the 0.6 cutoff.

PM2_Supporting

Absent in gnomAD v2.1.1 and v3.1.

PM5

Evidence from this curation has been used in PM5 for the classification of another variant at the same codon, Leu318Arg. Therefore, PM5 is not applied in order o avoid circularity

PM1

Variant is not within 3, 4 or 5.

Curation History

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