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_000132.4(F8):c.6305G>A (p.Gly2102Asp)

CA414900171

1163208 (ClinVar)

Gene: F8 (HGNC:2157)

Condition: hemophilia A (MONDO:0010602)

Inheritance Mode: X-linked inheritance

UUID: 445032ae-201c-47eb-be4a-4f11a33e5338

Approved on: 2026-04-10

Published on: 2026-04-12

HGVS expressions

NM_000132.4:c.6305G>A

NM_000132.4(F8):c.6305G>A (p.Gly2102Asp)

NC_000023.11:g.154896201C>T

CM000685.2:g.154896201C>T

NC_000023.10:g.154124476C>T

CM000685.1:g.154124476C>T

NC_000023.9:g.153777670C>T

NG_011403.1:g.131523G>A

NG_011403.2:g.131523G>A

ENST00000360256.9:c.6305G>A

ENST00000360256.8:c.6305G>A

NM_000132.3:c.6305G>A

Likely Pathogenic

PS4_Moderate PP4_Moderate PP3 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 F8 Version 2.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Coagulation Factor Deficiency VCEP

The c.6305G>A variant in F8 is a missense variant predicted to cause substitution of aspartic acid for glycine at amino acid 2102. This variant is completely absent from gnomAD v4.1.1 meeting PM2_Supporting. The missense variant has a REVEL score of 0.877 (>0.6) meeting PP3. At least 3 probands from the literature and internal laboratory data meet F8 phenotype criteria for PS4_Moderate and PP4_Moderate (PMID: 23926300, 29296726 & 23913812). In summary, based on the evidence available at this time, this variant is classified as likely pathogenic for hemophilia A. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel v2.0.0: PP4_Moderate, PS4_Moderate, PP3, PM2_Supporting.

PS4_Moderate

Two probands with mild hemophilia with factor VIII activity levels at 20% meeting PS4_Moderate (PMID: 23913812 & 23926300).

PP4_Moderate

Variant identified in proband with 3% factor VIII activity level in MLOF study.

PP3

REVEL score is 0.877, which above the 0.6 cutoff. SpliceAI prediction for donor gain = 0.01 and 0 for others.

PM2_Supporting

Variant is absent in gnomAD v4.1.1.

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.