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_019863.3:c.137T>A

CA414907101

Gene: F8 (HGNC:2157)

Condition: hemophilia A (MONDO:0010602)

Inheritance Mode: X-linked inheritance

UUID: ff4d31f3-17cd-4752-b167-53383dd6a07b

Approved on: 2025-10-03

Published on: 2025-10-07

HGVS expressions

NM_019863.3:c.137T>A

NC_000023.11:g.154863115A>T

CM000685.2:g.154863115A>T

NC_000023.10:g.154091390A>T

CM000685.1:g.154091390A>T

NC_000023.9:g.153744584A>T

NG_011403.1:g.164609T>A

NG_011403.2:g.164609T>A

ENST00000360256.9:c.6542T>A

ENST00000644698.1:c.275T>A

ENST00000330287.10:c.137T>A

ENST00000360256.8:c.6542T>A

NM_000132.3:c.6542T>A

NM_019863.2:c.137T>A

NM_000132.4:c.6542T>A

Likely Pathogenic

PM2_Supporting PS4_Moderate PP3 PP4_Moderate

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 F8 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Coagulation Factor Deficiency VCEP

The c.6542T>A (p.Leu2181His) variant is absent from males in population databases (gnomAD v2.1.1/gnomAD v3) meeting PM2_Supporting. The c.6542T>A (p.Leu2181His) missense variant has a REVEL score of 0.936 (>0.6) meeting PP3. The variant has been reported in at least 3 probands meeting phenotypic criteria for F8 meeting PS4_Moderate and PP4_Moderate (PMID: 29296726). 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 F8/F9: PM2_Supporting, PP3, PS4_Moderate, and PP4_Moderate.

PM2_Supporting

The c.6542T>A (p.Leu2181His) variant is absent from males in population databases (gnomAD v2.1.1/gnomAD v3).

PS4_Moderate

The c.6542T>A (p.p.Leu2181His) variant has been reported in 3 probands (1-3 probands & 0 gnomAD alleles) meeting phenotypic criteria for F8.

PP3

The c.6542T>A (p.Leu2181His) missense variant has a REVEL score of 0.936 (>0.6) and a CADD score of 26.3 (>21).

PP4_Moderate

There is at least 1 proband with severe Hemophilia A, meeting phenotypic criteria for F8.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.